Miracle-dz/UniFAR-FTUs huggingface dataset:
RAD51 Inhibition Induces R-Loop Formation in Early G1 Phase of the Cell Cycle

R-loops are three-stranded structures generated by annealing of nascent transcripts to the template DNA strand, leaving the non-template DNA strand exposed as a single-stranded loop. Although R-loops play important roles in physiological processes such as regulation of gene expression, mitochondrial DNA replication, or immunoglobulin class switch recombination, dysregulation of the R-loop metabolism poses a threat to the stability of the genome. A previous study in yeast has shown that the homologous recombination machinery contributes to the formation of R-loops and associated chromosome instability. On the contrary, here, we demonstrate that depletion of the key homologous recombination factor, RAD51, as well as RAD51 inhibition by the B02 inhibitor did not prevent R-loop formation induced by the inhibition of spliceosome assembly in human cells. However, we noticed that treatment of cells with B02 resulted in RAD51-dependent accumulation of R-loops in an early G1 phase of the cell cycle accompanied by a decrease in the levels of chromatin-bound ORC2 protein, a component of the pre-replication complex, and an increase in DNA synthesis. Our results suggest that B02-induced R-loops might cause a premature origin firing.
Au@Pt Core-Shell Nanoparticle Bioconjugates for the Therapy of HER2+ Breast Cancer and Hepatocellular Carcinoma. Model Studies on the Applicability of 193mPt and 195mPt Radionuclides in Auger Electron Therapy

193mPt and 195mPt radionuclides are therapeutically attractive Auger electron emitters with notably high Auger electron yield per decay. The present paper summarizes the first step of research on the applications of core-shell (Au@Pt) nanoparticles for electron Auger therapy of HER2+ (human epidermal growth factor receptor 2) breast cancer and hepatocellular carcinoma. Gold nanoparticles (30 nm) were synthesized covered with a platinum shell at high efficiency (>80%) and were further evaluated for in vitro studies such as binding affinity, internalization and cytotoxicity. To find the mechanism(s) responsible for platinum cytotoxicity in HepG2 cells, the platinum concentration in isolated cell nuclei and cytoplasm was determined using ICP-MS (inductively coupled plasma mass spectrometry). Lack of platinum in cell nuclei suggests that the cytotoxic effect is associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Studies carried out on the SKOV-3 cell line with the use of a synthesized targeting bioconjugate (Au@Pt-PEG-trastuzumab) revealed a high affinity of this preparation to HER2+ cells, its internalization, its placement in the perinuclear area and partial intranuclear location. The specific binding for HER2 negative cells, MDA-MB-231, was negligible and Au@Pt-PEG-trastuzumab did not enter these cells. The results obtained are promising and warrant future investigation of Auger electron therapy using 193mPt and 195mPt based radiopharmaceuticals.
Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance

Antimicrobial drugs are key tools to prevent and treat bacterial infections. Despite the early success of antibiotics, the current treatment of bacterial infections faces serious challenges due to the emergence and spread of resistant bacteria. Moreover, the decline of research and private investment in new antibiotics further aggravates this antibiotic crisis era. Overcoming the complexity of antimicrobial resistance must go beyond the search of new classes of antibiotics and include the development of alternative solutions. The evolution of nanomedicine has allowed the design of new drug delivery systems with improved therapeutic index for the incorporated compounds. One of the most promising strategies is their association to lipid-based delivery (nano)systems. A drug’s encapsulation in liposomes has been demonstrated to increase its accumulation at the infection site, minimizing drug toxicity and protecting the antibiotic from peripheral degradation. In addition, liposomes may be designed to fuse with bacterial cells, holding the potential to overcome antimicrobial resistance and biofilm formation and constituting a promising solution for the treatment of potential fatal multidrug-resistant bacterial infections, such as methicillin resistant Staphylococcus aureus. In this review, we aim to address the applicability of antibiotic encapsulated liposomes as an effective therapeutic strategy for bacterial infections.
Polypurine Reverse-Hoogsteen Hairpins as a Tool for Exon Skipping at the Genomic Level in Mammalian Cells

Therapeutic strategies for rare diseases based on exon skipping are aimed at mediating the elimination of mutated exons and restoring the reading frame of the affected protein. We explored the capability of polypurine reverse-Hoogsteen hairpins (PPRHs) to cause exon skipping in NB6 cells carrying a duplication of exon 2 of the DHFR gene that causes a frameshift abolishing DHFR activity. Methods: Different editing PPRHs were designed and transfected in NB6 cells followed by incubation in a DHFR-selective medium lacking hypoxanthine and thymidine. Surviving colonies were analyzed by DNA sequencing, RT-PCR, Western blotting and DHFR enzymatic activity. Results: Transfection of editing PPRHs originated colonies in the DHFR-selective medium. DNA sequencing results proved that the DHFR sequence in all these colonies corresponded to the wildtype sequence with just one copy of exon 2. In the edited colonies, the skipping of the additional exon was confirmed at the mRNA level, the DHFR protein was restored, and it showed high levels of DHFR activity. Conclusions: Editing-PPRHs are able to cause exon skipping at the DNA level and could be applied as a possible therapeutic tool for rare diseases.
5G Numerologies Assessment for URLLC in Industrial Communications

The fifth-generation (5G) network is presented as one of the main options for Industry 4.0 connectivity. Ultra-Reliable and Low Latency Communications (URLLC) is the 5G service category used by critical mechanisms, with a millisecond end-to-end delay and reduced probability of failure. 5G defines new numerologies, together with mini-slots for a faster scheduling. The main challenge of this is to select the appropriate numerology according to radio conditions. This fact is very important in industrial scenarios, where the fundamental problems are interference and multipath propagation, due to the presence of concrete walls and large metallic machinery and structures. Therefore, this paper is focused on analyzing the impact of the numerology selection on the delay experienced at radio link level for a remote-control service. The study, which has been carried out in a simulated cellular factory environment, has been performed for different packet sizes and channel conditions, focusing on outliers. Evaluation results show that not always a higher numerology, with a shorter slot duration, is appropriate for this type of service, particularly under Non-Line-of-Sight (NLOS) conditions.
Extra-Soft Tactile Sensor for Sensitive Force/Displacement Measurement with High Linearity Based on a Uniform Strength Beam

The soft sensing system has drawn huge enthusiasm for the application of soft robots and healthcare recently. Most of them possess thin-film structures that are beneficial to monitoring strain and pressure, but are unfavorable for measuring normal displacement with high linearity. Here we propose soft tactile sensors based on uniform-strength cantilever beams that can be utilized to measure the normal displacement and force of soft objects simultaneously. First, the theoretical model of the sensors is constructed, on the basis of which, the sensors are fabricated for testing their sensing characteristics. Next, the test results validate the constructed model, and demonstrate that the sensors can measure the force as well as the displacement. Besides, the self-fabricated sensor can have such prominent superiorities as follows—it is ultra-soft, and its equivalent stiffness is only 0.31 N·m−1 (approximately 0.4% of fat); it has prominent sensing performance with excellent linearity (R2 = 0.999), high sensitivity of 0.533 pF·mm−1 and 1.66 pF·mN−1 for measuring displacement and force; its detection limit is as low as 70 μm and 20 μN that is only one-tenth of the touch of a female fingertip. The presented sensor highlights a new idea for measuring the force and displacement of the soft objects with broad application prospects in mechanical and medical fields.
Role of Rho GTPase Interacting Proteins in Subcellular Compartments of Podocytes

The first step of urine formation is the selective filtration of the plasma into the urinary space at the kidney structure called the glomerulus. The filtration barrier of the glomerulus allows blood cells and large proteins such as albumin to be retained while eliminating the waste products of the body. The filtration barrier consists of three layers: fenestrated endothelial cells, glomerular basement membrane, and podocytes. Podocytes are specialized epithelial cells featured by numerous, actin-based projections called foot processes. Proteins on the foot process membrane are connected to the well-organized intracellular actin network. The Rho family of small GTPases (Rho GTPases) act as intracellular molecular switches. They tightly regulate actin dynamics and subsequent diverse cellular functions such as adhesion, migration, and spreading. Previous studies using podocyte-specific transgenic or knockout animal models have established that Rho GTPases are crucial for the podocyte health and barrier function. However, little attention has been paid regarding subcellular locations where distinct Rho GTPases contribute to specific functions. In the current review, we discuss cellular events involving the prototypical Rho GTPases (RhoA, Rac1, and Cdc42) in podocytes, with particular focus on the subcellular compartments where the signaling events occur. We also provide our synthesized views of the current understanding and propose future research directions.
Quality of Life with Vulvar Carcinoma Treated with Palliative Electrochemotherapy: The ELECHTRA (ELEctroCHemoTherapy vulvaR cAncer) Study

Simple Summary A multicenter prospective observational study was conducted on patients with vulvar cancer (VC) refractory or not amenable to standard therapies undergoing palliative electrochemotherapy (ECT) as per clinical practice. Electrochemotherapy with bleomycin improves quality of life in patients with recurrent vulvar cancer. The assessment was performed with a visual analog pain scale (VAS), EuroQol 5-Dimension 5-Level (EQ-5D-L5) and Functional Assessment of Cancer Therapy—Vulva cancer (FACT—V). To our knowledge, this is the first study reporting the impact of palliative ECT on QoL of VC patients, with a detailed evaluation of potential correlations between tumor characteristics and severity of and response to symptoms. This improvement is higher in patients with clinical response and for smaller and anterior lesions. Based on these results, ECT in VC should be considered as an effective option based on the favorable outcomes both in terms of response and QoL. Abstract The ELECHTRA (ELEctroChemoTherapy vulvaR cAncer) project was conceived to collect data on palliative electrochemotherapy (ECT) in vulvar cancer (VC) assessing patients’ outcomes (response and survival) and impact on quality of life (QoL). After reporting outcome data in 2019, here, we present the results on QoL. A multicenter prospective observational study was conducted on patients with VC refractory or not amenable to standard therapies undergoing palliative ECT as per clinical practice. The following questionnaires were administered before and after ECT (two and four months later, early and late follow-up): visual analog pain scale (VAS), EuroQol 5-Dimension 5-Level (EQ-5D-L5) and Functional Assessment of Cancer Therapy—Vulva cancer (FACT—V). Analyses were conducted on both the whole study population and by subgroups (clinical response after ECT and site, number and size of lesions). Questionnaires from 55 patients were evaluated. Compared to the baseline (6.1 ± 2.1), the VAS was significantly reduced at early (4.3 ± 2.5) and late follow-up (4.6 ± 2.8) (p < 0.0001). The FACT—V score improved significantly at early (9.6 ± 4.0) (p < 0.0001) and late follow-up (8.9 ± 4.1) (p < 0.0054) as compared to the baseline (7.1 ± 3.6). No EQ-5D-5L statistically significant changes were observed. Subgroup analyses showed worse QoL in patients with stable or progressive disease, posterior site and multiple or larger than 3 cm nodules. This is the first study reporting improved QoL in VC patients after palliative ECT. Based on these results, ECT in VC should be considered an effective option based on the favorable outcomes both in terms of response and QoL.
Enhancement of the Thermal Performance of the Paraffin-Based Microcapsules Intended for Textile Applications

Phase changing materials (PCMs) microcapsules MPCM32D, consisting of a polymeric melamine-formaldehyde (MF) resin shell surrounding a paraffin core (melting point: 30–32 °C), have been modified by introducing thermally conductive additives on their outer shell surface. As additives, multiwall carbon nanotubes (MWCNTs) and poly (3,4-ethylenedioxyoxythiophene) poly (styrene sulphonate) (PEDOT: PSS) were used in different parts by weight (1 wt.%, 5 wt.%, and 10 wt.%). The main aim of this modification—to enhance the thermal performance of the microencapsulated PCMs intended for textile applications. The morphologic analysis of the newly formed coating of MWCNTs or PEDOT: PSS microcapsules shell was observed by SEM. The heat storage and release capacity were evaluated by changing microcapsules MPCM32D shell modification. In order to evaluate the influence of the modified MF outer shell on the thermal properties of paraffin PCM, a thermal conductivity coefficient (λ) of these unmodified and shell-modified microcapsules was also measured by the comparative method. Based on the identified optimal parameters of the thermal performance of the tested PCM microcapsules, a 3D warp-knitted spacer fabric from PET was treated with a composition containing 5 wt. % MWCNTs or 5 wt. % PEDOT: PSS shell-modified microcapsules MPCM32D and acrylic resin binder. To assess the dynamic thermal behaviour of the treated fabric samples, an IR heating source and IR camera were used. The fabric with 5 wt. % MWCNTs or 5 wt. % PEDOT: PSS in shell-modified paraffin microcapsules MPCM32D revealed much faster heating and significantly slower cooling compared to the fabric treated with the unmodified ones. The thermal conductivity of the investigated fabric samples with modified microcapsules MPCM32D has been improved in comparison to the fabric samples with unmodified ones. That confirms the positive influence of using thermally conductive enhancing additives for the heat transfer rate within the textile sample containing these modified paraffin PCM microcapsules.
An Activatable T1-Weighted MR Contrast Agent: A Noninvasive Tool for Tracking the Vicinal Thiol Motif of Thioredoxin in Live Cells

We have synthesized new magnetic resonance imaging (MRI) T1 contrast agents (CA1 and CA2) that permit the activatable recognition of the cellular vicinal thiol motifs of the protein thioredoxin. The contrast agents showed MR relaxivities typical of gadolinium complexes with a single water molecule coordinated to a Gd3+ center (i.e., ~4.54 mM−1s−1) for both CA1 and CA2 at 60 MHz. The contrast agent CA1 showed a ~140% relaxivity enhancement in the presence of thioredoxin, a finding attributed to a reduction in the flexibility of the molecule after binding to thioredoxin. Support for this rationale, as opposed to one based on preferential binding, came from 1H-15N-HSQC NMR spectral studies; these revealed that the binding affinities toward thioredoxin were almost the same for both CA1 and CA2. In the case of CA1, T1-weighted phantom images of cancer cells (MCF-7, A549) could be generated based on the expression of thioredoxin. We further confirmed thioredoxin expression-dependent changes in the T1-weighted contrast via knockdown of the expression of the thioredoxin using siRNA-transfected MCF-7 cells. The nontoxic nature of CA1, coupled with its relaxivity features, leads us to suggest that it constitutes a first-in-class MRI T1 contrast agent that allows for the facile and noninvasive monitoring of vicinal thiol protein motif expression in live cells.
QuEChERS LC–MS/MS Screening Method for Mycotoxin Detection in Cereal Products and Spices

We developed and validated a screening method for mycotoxin analysis in cereal products and spices. Ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS/MS) was used for the analysis. Dispersive solid-phase extractions (d-SPEs) were used for the extraction of samples. Ochratoxin A (OTA), zearalenone (ZEA), aflatoxins (AFLA; AFB1, AFB2, AFG1, AFG2), deoxynivalenol (DON), fumonisin (FUMO; FB1, FB2, FB3), T2, and HT2 were validated in maize. AFLA and DON were validated in black pepper. The method satisfies the requirements of Commission Regulation (EC) no. 401/2006 and (EC) no. 1881/2006. The screening target concentration (STC) was under maximum permitted levels (MLs) for all mycotoxins validated. The method’s performance was assessed by two different proficiencies and tested with 100 real samples.
Evaluation of Late Postural Complications in Breast Cancer Patients Undergoing Breast-Conserving Therapy in Relation to the Type of Axillary Intervention-Cross-Sectional Study

Purpose: The aim of the study was to evaluate posture in patients undergoing breast-conserving therapy (BCT) in relation to the type of surgical intervention to the axilla. Methods: The study was conducted on patients who had undergone breast-conserving surgical treatment for breast cancer 5–6 years earlier. In 54 patients, BCT+ALND (axillary lymph node dissection) was performed, while 63 patients were subjected to BCT+SLND (sentinel lymph node dissection). The control group consisted of 54 females. The study was conducted using digital postural assessment. Results: No statistically significant differences were observed with respect to the parameters between the BCT+SLNB and BCT+ALND groups (p > 0.05). However, the differences were highly significant between the CG (control group) and the studied groups (BCT+ALND, BCT+SLNB) for the following parameters: BETA angle of thoracolumbar spine inclination (p = 0.002), GAMMA angle of thoracic spine inclination (p = 0.0044), TKA (thoracic kyphosis angle) (p < 0.0001) and shoulder level inclination (p = 0.0004). The BCT+ALND patients were characterized by higher dependency of raised shoulder (p = 0.0028) and inferior angle of the scapula (p = 0.00018) on the operated side compared to BCT+SLNB patients. Conclusions: Postural imbalance occurs independent of the type of axillary intervention. Disturbances within the upper torso (abnormal position of shoulders and inferior angles of scapulae) are more pronounced in patients after ALND.
DNA Methylation Patterns Correlate with the Expression of SCNN1A, SCNN1B, and SCNN1G (Epithelial Sodium Channel, ENaC) Genes

The interplay between the cystic fibrosis transmembrane conductance regulator (CFTR) and the epithelial sodium channel (ENaC) in respiratory epithelia has a crucial role in the pathogenesis of cystic fibrosis (CF). The comprehension of the mechanisms of transcriptional regulation of ENaC genes is pivotal to better detail the pathogenic mechanism and the genotype–phenotype relationship in CF, as well as to realize therapeutic approaches based on the transcriptional downregulation of ENaC genes. Since we aimed to study the epigenetic transcriptional control of ENaC genes, an assessment of their expression and DNA methylation patterns in different human cell lines, nasal brushing samples, and leucocytes was performed. The mRNA expression of CFTR and ENaC subunits α, β and γ (respectively SCNN1A, SCNN1B, and SCNN1G genes) was studied by real time PCR. DNA methylation of 5′-flanking region of SCNN1A, SCNN1B, and SCNN1G genes was studied by HpaII/PCR. The levels of expression and DNA methylation of ENaC genes in the different cell lines, brushing samples, and leukocytes were very variable. The DNA regions studied of each ENaC gene showed different methylation patterns. A general inverse correlation between expression and DNA methylation was evidenced. Leukocytes showed very low expression of all the 3 ENaC genes corresponding to a DNA methylated pattern. The SCNN1A gene resulted to be the most expressed in some cell lines that, accordingly, showed a completely demethylated pattern. Coherently, a heavy and moderate methylated pattern of, respectively, SCNN1B and SCNN1G genes corresponded to low levels of expression. As exceptions, we found that dexamethasone treatment appeared to stimulate the expression of all the 3 ENaC genes, without an evident modulation of the DNA methylation pattern, and that in nasal brushing a considerable expression of all the 3 ENaC genes were found despite an apparent methylated pattern. At least part of the expression modulation of ENaC genes seems to depend on the DNA methylation patterns of specific DNA regions. This points to epigenetics as a controlling mechanism of ENaC function and as a possible therapeutic approach for CF.
How Self-Control Predicts Moral Decision Making: An Exploratory Study on Healthy Participants

Research on moral reasoning calls into question self-control, which encompasses impulsivity, compulsivity, and inhibitory control. However, a thorough investigation exploring how these three dimensions can affect moral reasoning in response to different scenarios is unavailable. We addressed this topic by testing the predictive role of these three dimensions of self-control on appraisals for ethical violations related with different types of scenarios. Overall, our results suggest that all three dimensions of self-control are involved in moral reasoning, depending on the type of appraisal and provided moral scenarios.
Characterization of Hybrid Materials Prepared by Sol-Gel Method for Biomedical Implementations. A Critical Review

The interaction between tissues and biomaterials (BM) has the purpose of improving and replacing anatomical parts of the human body, avoiding the occurrence of adverse reactions in the host organism. Unfortunately, the early failure of implants cannot be currently avoided, since neither a good mixture of mechanical and chemical characteristics of materials nor their biocompatibility has been yet achieved. Bioactive glasses are recognized to be a fine class of bioactive substances for good repair and replacement. BM interact with living bones through the formation of a hydroxyapatite surface layer that is analogous to bones. Bioglasses’ composition noticeably affects their biological properties, as does the synthesis method, with the best one being the versatile sol-gel technique, which includes the change of scheme from a ‘sol’ fluid into a ‘gel’. This process is widely used to prepare many materials for biomedical implants (e.g., hip and knee prostheses, heart valves, and ceramic, glassy and hybrid materials to serve as carriers for drug release). Nanoparticles prepared by the sol-gel method are interesting systems for biomedical implementations, and particularly useful for cancer therapy. This review provides many examples concerning the synthesis and characterization of the above-mentioned materials either taken from literature and from recently prepared zirconia/polyethylene glycol (PEG) hybrids, and the corresponding results are extensively discussed.