Miracle-dz/UniFAR-FTUs huggingface dataset:
Development and Evaluation of Polyvinylpyrrolidone K90 and Poloxamer 407 Self-Assembled Nanomicelles: Enhanced Topical Ocular Delivery of Artemisinin

Age-related macular degeneration is a multifactorial disease affecting the posterior segment of the eye and is characterized by aberrant nascent blood vessels that leak blood and fluid. It ends with vision loss. In the present study, artemisinin which is poorly water-soluble and has potent anti-angiogenic and anti-inflammatory properties was formulated into nanomicelles and characterized for its ocular application and anti-angiogenic activity using a CAM assay. Artemisinin-loaded nanomicelles were prepared by varying the concentrations of PVP k90 and poloxamer 407 at different ratios and showed spherical shape particles in the size range of 41–51 nm. The transparency and cloud point of the developed artemisinin-loaded nanomicelles was found to be 99–94% and 68–70 °C, respectively. The in vitro release of artemisinin from the nanomicelles was found to be 96.0–99.0% within 8 h. The trans-corneal permeation studies exhibited a 1.717–2.169 µg permeation of the artemisinin from nanomicelles through the excised rabbit eye cornea for 2 h. Drug-free nanomicelles did not exhibit noticeable DNA damage and showed an acceptable level of hemolytic potential. Artemisinin-loaded nanomicelles exhibited remarkable anti-angiogenic activity compared to artemisinin suspension. Hence, the formulated artemisinin-loaded nanomicelles might have the potential for the treatment of AMD.
Cardiorespiratory Fitness and Muscular Strength Moderates the Relationship between FNDC5 Polymorphism and Adiposity in Children and Adolescents

The human locus FNDC5 rs16835198 contributes positively to anthropometric phenotypes in children and adolescents. However, the role of specific components of physical fitness in this relationship is not known. The present study aimed to verify the moderator role of cardiorespiratory fitness (CRF) and muscular strength in the relationship between rs16835198 polymorphism FNDC5 and adiposity in children and adolescents. This cross-sectional study was carried out by genotyping the rs16835198 FNDC5 polymorphism in 1701 children and adolescents (mean age 11.73 ± 2.75 years). Obesity was assessed using waist circumference and body mass index (BMI) z-scores. To evaluate CRF and muscular strength, the 6 min run/walk test and lower limb strength (LLS) were used. Linear regression models were applied, and all analyses were adjusted for age, sex, skin color, living area, and school type. A significant interaction term for CRF (p = 0.038) and LLS (p = 0.040) × rs16835198 FNDC5 with WC was identified. Regarding BMI, a significant interaction term for CRF (p = 0.007) and LLS (p = 0.044) × rs16835198 FNDC5 was observed. Moreover, medium and high CRF and LLS levels protected against higher WC and BMI. In conclusion, adiposity levels of children and adolescents with a genetic predisposition to obesity might be modified by improving CRF and muscular strength.
Preventing and Monitoring Work-Related Diseases in Firefighters: A Literature Review on Sensor-Based Systems and Future Perspectives in Robotic Devices

In recent years, the necessity to prevent work-related diseases has led to the use of sensor-based systems to measure important features during working activities. This topic achieved great popularity especially in hazardous and demanding activities such as those required of firefighters. Among feasible sensor systems, wearable sensors revealed their advantages in terms of possibility to conduct measures in real conditions and without influencing the movements of workers. In addition, the advent of robotics can be also exploited in order to reduce work-related disorders. The present literature review aims at providing an overview of sensor-based systems used to monitor physiological and physical parameters in firefighters during real activities, as well as to offer ideas for understanding the potentialities of exoskeletons and assistive devices.
Cep192, a Novel Missing Link between the Centrosomal Core and Corona in Dictyostelium Amoebae

The Dictyostelium centrosome is a nucleus-associated body with a diameter of approx. 500 nm. It contains no centrioles but consists of a cylindrical layered core structure surrounded by a microtubule-nucleating corona. At the onset of mitosis, the corona disassembles and the core structure duplicates through growth, splitting, and reorganization of the outer core layers. During the last decades our research group has characterized the majority of the 42 known centrosomal proteins. In this work we focus on the conserved, previously uncharacterized Cep192 protein. We use superresolution expansion microscopy (ExM) to show that Cep192 is a component of the outer core layers. Furthermore, ExM with centrosomal marker proteins nicely mirrored all ultrastructurally known centrosomal substructures. Furthermore, we improved the proximity-dependent biotin identification assay (BioID) by adapting the biotinylase BioID2 for expression in Dictyostelium and applying a knock-in strategy for the expression of BioID2-tagged centrosomal fusion proteins. Thus, we were able to identify various centrosomal Cep192 interaction partners, including CDK5RAP2, which was previously allocated to the inner corona structure, and several core components. Studies employing overexpression of GFP-Cep192 as well as depletion of endogenous Cep192 revealed that Cep192 is a key protein for the recruitment of corona components during centrosome biogenesis and is required to maintain a stable corona structure.
Fine Carbohydrate Structure of Dietary Resistant Glucans Governs the Structure and Function of Human Gut Microbiota

Increased dietary fiber consumption has been shown to increase human gut microbial diversity, but the mechanisms driving this effect remain unclear. One possible explanation is that microbes are able to divide metabolic labor in consumption of complex carbohydrates, which are composed of diverse glycosidic linkages that require specific cognate enzymes for degradation. However, as naturally derived fibers vary in both sugar composition and linkage structure, it is challenging to separate out the impact of each of these variables. We hypothesized that fine differences in carbohydrate linkage structure would govern microbial community structure and function independently of variation in glycosyl residue composition. To test this hypothesis, we fermented commercially available soluble resistant glucans, which are uniformly composed of glucose linked in different structural arrangements, in vitro with fecal inocula from each of three individuals. We measured metabolic outputs (pH, gas, and short-chain fatty acid production) and community structure via 16S rRNA amplicon sequencing. We determined that community metabolic outputs from identical glucans were highly individual, emerging from divergent initial microbiome structures. However, specific operational taxonomic units (OTUs) responded similarly in growth responses across individuals’ microbiota, though in context-dependent ways; these data suggested that certain taxa were more efficient in competing for some structures than others. Together, these data support the hypothesis that variation in linkage structure, independent of sugar composition, governs compositional and functional responses of microbiota.
Effects of Six-Week Resistance Training with or without Vibration on Metabolic Markers of Bone Metabolism

Acute and protracted effects of resistive exercise (RE) and resistive exercise with whole-body vibration (RVE) on metabolic markers of bone metabolism were investigated. Twenty-six men participated in a randomized training program including RE (n = 13; age = 23.4 ± 1.4 years) or RVE (n = 13; age = 24.3 ± 3.3 years). During the first session, acute C-terminal telopeptide of type I collagen (CTX) responses decreased by 12.9% (standard deviation, SD 13.7%) after 2 min, followed by a 15.5% (SD 36.0%) increase at 75 min after exercise (both p < 0.001). Procollagen type I amino terminal propeptide (P1NP) increased by 12.9% (SD 9.1%) at 2 min (p < 0.001) but no change occurred at 75 min. Sclerostin showed prolonged responses from 2 to 75 min post-exercise in the first session (p < 0.001). Acute responses at the first session were comparable between groups for CTX and P1NP, acute sclerostin responses were substantially greater in RE than in RVE (p = 0.003). No significant differences were noted in the resting baseline levels of CTX, P1NP, or sclerostin from the beginning to the end of the six-week progressive training. The present study therefore did not demonstrate any sizeable enhancement of bone turnover that could match the effects that have been repeatably made in response to countermeasure exercise during bed rest.
The Effect of Primary and Middle School Teachers’ Problematic Internet Use and Fear of COVID-19 on Psychological Need Thwarting of Online Teaching and Psychological Distress

Problematic Internet use (PIU) is a risk factor for psychological distress during COVID-19, as teachers are a psychologically vulnerable population. We explored the role of PIU in terms of primary and middle school teachers’ fear of COVID-19 and psychological need thwarting (PNT) of online teaching. We empirically evaluated the relationships among these research variables in explaining teachers’ psychological distress during COVID-19. Online survey data were collected from 9030 teachers. A high proportion of participants demonstrated psychological distress: depression (20.4%), anxiety (26.4%), and stress (10.2%). Structural equation modeling was used to test our proposed conceptual model, wherein PIU behaviors served as predictors, mediated by fear of COVID-19 and PNT of online teaching, for teachers’ psychological distress. With ideal model fit, the results of the path coefficients indicated that PIU behaviors were associated with fear of COVID-19 (p < 0.001); fear of COVID-19 and PNT of online teaching were associated with psychological distress (p < 0.001); and fear of COVID-19 was also positively associated with PNT of online teaching (p < 0.001). PSU and PSMU had an indirect positive effect on psychological distress through the mediator of fear of COVID-19 and PNT of online teaching. As such, we suggest that school administrators pay greater attention to teachers’ psychological needs through efforts to enhance teachers’ autonomy and relatedness from interpersonal relationships, alleviating PNT of online teaching. Our PNT of online teaching scale may also serve as a contribution for further research and practice.
Circulating P2X7 Receptor Signaling Components as Diagnostic Biomarkers for Temporal Lobe Epilepsy

Circulating molecules have potential as biomarkers to support the diagnosis of epilepsy and to assist with differential diagnosis, for example, in conditions resembling epilepsy, such as in psychogenic non-epileptic seizures (PNES). The P2X7 receptor (P2X7R) is an important regulator of inflammation and mounting evidence supports its activation in the brain during epilepsy. Whether the P2X7R or P2X7R-dependent signaling molecules can be used as biomarkers of epilepsy has not been reported. P2X7R levels were analyzed by quantitative ELISA using plasma samples from controls and patients with temporal lobe epilepsy (TLE) or PNES. Moreover, blood cell P2X7R expression and P2X7R-dependent cytokine signature was measured following status epilepticus in P2X7R-EGFP reporter, wildtype, and P2X7R-knockout mice. P2X7R plasma levels were higher in TLE patients when compared with controls and patients with PNES. Plasma levels of the broad inflammatory marker protein C-Reactive protein (CRP) were similar between the three groups. Using P2X7R-EGFP reporter mice, we identified monocytes as the main blood cell type expressing P2X7R after experimentally evoked seizures. Finally, cytokine array analysis in P2X7R-deficient mice identified KC/GRO as a potential P2X7R-dependent plasma biomarker following status epilepticus and during epilepsy. Our data suggest that P2X7R signaling components may be a promising subclass of circulating biomarkers to support the diagnosis of epilepsy.
Physical Activity Reduction and the Worsening of Gastrointestinal Health Status during the Second COVID-19 Home Confinement in Southern Italy

Due to the COVID-19 pandemic, in December 2020, the Italian government established a second home confinement during the Christmas holidays. These restrictions offered the opportunity to utilize a well-defined model for observing the consequences of lifestyle changes of healthy individuals. This study aimed at estimating in healthy subjects from Southern Italy the physical activity (PA), the presence and the severity of gastrointestinal (GI) symptoms, and the association between the possible worsening of GI health status and the PA levels. An adapted version of the International PA Questionnaire-short form (IPAQ-SF) and the Gastrointestinal Symptom Rating Scale (GSRS) were proposed through Google’s online survey platform in three different periods via WhatsAppTM to 499 healthy subjects (62% females) from Apulia (25%), Calabria (37%), and Campania (38%). Our results showed statistically significant changes during the home confinement: reduced energy expenditure (EE) among overweight subjects (−239.82, 95%CI −405.74; −73.89) or those who had high GSRS total score (−1079.54, 95%CI −2027.43; −131.66). An increase in GSRS total score was observed in overweight subjects, reaching statistical significance in those from Campania. Our study supports the importance of PA to reduce health risks, including those related to the possible onset of GI tract diseases.
Powder Fever and Its Impact on Decision-Making in Avalanche Terrain

We examined the effect of emotions, associated with “powder fever”, on decision-making in avalanche terrain. Background: Skiing in avalanche terrain is a voluntary activity that exposes the participant to potentially fatal risk. Impaired decision-making in this context can therefore have devastating results, often with limited prior corrective feedback and learning opportunities. Previous research has suggested that arousal caused by emotions affects risk assessment and intentions to engage in risky behavior. We propose that powder fever may induce similar responses. Methods: We used the following two experimental methods: laboratory studies with visual visceral stimuli (ski movies) and a field study with real stimuli (skiing exciting terrain). We evaluated the effect of emotions on attention, risk assessment, and willingness to expose oneself and others to risk. Results: Both the laboratory studies and the field study showed that skiing-related stimuli had a relatively strong effect on reported emotions. However, we found very few significant effects on decision-making or assessment of risk. Conclusions: Skiing activities make people happier. However, despite the clear parallels to sexual arousal, powder fever does not appear to significantly impair decision-making in our study. More research on the effects of powder fewer on milder forms of risk-taking behavior is needed.
Changes in Antibiotic-Resistance Genes Induced by the Grazing Effect in Three Cladoceran Species

The acquisition of Antibiotic-Resistance Genes (ARGs) by natural bacteria caused by antibiotic abuse is causing serious problems for human and animal welfare. Here, we evaluated the influence of three cladoceran species on Antibiotic-Resistant Bacteria (ARB) and tetracycline-resistance gene (tet(A)) copies, and discussed the effect of these biological interactions on the distribution and diffusion of ARGs in freshwater ecosystems. Bacterial community and tet(A) abundances in water samples collected from wetlands were strongly influenced by cladoceran presence. The presence of Daphnia obtusa dramatically decreased ARB and tet(A) abundance compared to that with other cladoceran species (Chydorus sphaericus and Simocephalus vetulus). Interestingly, we found a high abundance of Flavobacteriales in the microbiomes of cladoceran species. Considering that Flavobacteriales species are potential carriers of the tet(A) gene, their adsorption and assimilation with cladocerans could significantly impact the reduction of tet(A) in water. Field surveys also showed that tet(A) abundance could be low if the dominance of D. obtusa in each wetland was high. This study highlighted the need for ecological interactions and a broad range of niches in the food web when discussing the fate of ARGs in freshwater ecosystems.
Applicability Domain of QSAR models

In recent decades, computational models have gained popularity for predictions of biological activities and physico-chemical properties. The major limiting point of computational models is a lack for a clear definition of their applicability domain. The work introduces the methodology for the AD assessment and performs a comprehensive benchmarking analysis of existing and new approaches. The practical AD assessment is demonstrated in a number of studies on the prediction of such properties as mutagenicity (Ames test), toxicity (inhibition growth concentration), lipophilicity and cytochromes inhibition. It is shown that the AD approaches allow to estimate the prediction accuracy for every compound individually and, thereby, to identify highly accurate predictions with the accuracy close to that of experimental measurements. All the introduced AD methods are implemented as a part of a new platform for chemical modeling (OCHEM) and are publicly available online at http://ochem.eu.
Unexpected Fluorescence Emission Behaviors of Tetraphenylethylene-Functionalized Polysiloxane and Highly Reversible Sensor for Nitrobenzene

Tetraphenylethylene (TPE), a typical luminogen with aggregation-induced emission (AIE) features, has been widely used to prepare AIE fluorescent materials. In this study, TPE-functionalized polydimethylsiloxane (n-TPE-AP-PDMS) was successfully synthesized by attaching TPE to polydimethylsiloxane via aza-Michael addition. The introduction of polydimethylsiloxane to TPE had no obvious effect on photophysical properties. Intriguingly, n-TPE-AP-PDMS exhibited two opposite fluorescence emission behaviors in different systems: aggregation-induced quenching (ACQ) behavior in a tetrahydrofuran/water mixture and typical AIE phenomenon in a tetrahydrofuran/hexane mixture. This unexpected transition from ACQ to AIE can be attributed to a twisted intramolecular charge-transfer effect and flexible aminopropyl polydimethylsiloxane. n-TPE-AP-PDMS was further used as a fluorescent probe to detect nitrobenzene and it showed high quenching efficiency. Moreover, the n-TPE-AP-PDMS film showed high reversibility so that the quenching efficiency remained constant after five cycles. This work can provide a deeper understanding of AIE behavior and guidance to develop a new AIE polymer for chemosensors with high performance.
3D Printing of Pharmaceutical Application: Drug Screening and Drug Delivery

Advances in three-dimensional (3D) printing techniques and the development of tailored biomaterials have facilitated the precise fabrication of biological components and complex 3D geometrics over the past few decades. Moreover, the notable growth of 3D printing has facilitated pharmaceutical applications, enabling the development of customized drug screening and drug delivery systems for individual patients, breaking away from conventional approaches that primarily rely on transgenic animal experiments and mass production. This review provides an extensive overview of 3D printing research applied to drug screening and drug delivery systems that represent pharmaceutical applications. We classify several elements required by each application for advanced pharmaceutical techniques and briefly describe state-of-the-art 3D printing technology consisting of cells, bioinks, and printing strategies that satisfy requirements. Furthermore, we discuss the limitations of traditional approaches by providing concrete examples of drug screening (organoid, organ-on-a-chip, and tissue/organ equivalent) and drug delivery systems (oral/vaginal/rectal and transdermal/surgical drug delivery), followed by the introduction of recent pharmaceutical investigations using 3D printing-based strategies to overcome these challenges.
Antibiotics Used in Empiric Treatment of Ocular Infections Trigger the Bacterial Rcs Stress Response System Independent of Antibiotic Susceptibility

The Rcs phosphorelay is a bacterial stress response system that responds to envelope stresses and in turn controls several virulence-associated pathways, including capsule, flagella, and toxin biosynthesis, of numerous bacterial species. The Rcs system also affects antibiotic tolerance, biofilm formation, and horizontal gene transfer. The Rcs system of the ocular bacterial pathogen Serratia marcescens was recently demonstrated to influence ocular pathogenesis in a rabbit model of keratitis, with Rcs-defective mutants causing greater pathology and Rcs-activated strains demonstrating reduced inflammation. The Rcs system is activated by a variety of insults, including β-lactam antibiotics and polymyxin B. In this study, we developed three luminescence-based transcriptional reporters for Rcs system activity and used them to test whether antibiotics used for empiric treatment of ocular infections influence Rcs system activity in a keratitis isolate of S. marcescens. These included antibiotics to which the bacteria were susceptible and resistant. Results indicate that cefazolin, ceftazidime, polymyxin B, and vancomycin activate the Rcs system to varying degrees in an RcsB-dependent manner, whereas ciprofloxacin and tobramycin activated the promoter fusions, but in an Rcs-independent manner. Although minimum inhibitory concentration (MIC) analysis demonstrated resistance of the test bacteria to polymyxin B and vancomycin, the Rcs system was activated by sub-inhibitory concentrations of these antibiotics. Together, these data indicate that a bacterial stress system that influences numerous pathogenic phenotypes and drug-tolerance is influenced by different classes of antibiotics despite the susceptibility status of the bacterium.