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hanisms of age-related psychiatric/neurological disorders.Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of the corticospinal motor neurons, which ultimately leads to death. The repeat expansion in chromosome 9 open reading frame 72 (C9ORF72) represents the most common genetic cause of ALS and it is also involved in the pathogenesis of other neurodegenerative disorders. To offer insights into C9ORF72-mediated pathogenesis, we quantitatively analyzed the proteome of patient-derived primary skin fibroblasts from ALS patients carrying the C9ORF72 mutation compared with ALS patients who tested negative for it. Differentially expressed proteins were identified, used to generate a protein-protein interaction network and subjected to a functional enrichment analysis to unveil altered molecular pathways. ALS patients were also compared with patients affected by frontotemporal dementia carrying the C9ORF72 repeat expansion. As a result, we demonstrated that the molecular pathways mainly altered in fibroblasts (e.g., protein homeostasis) mirror the alterations observed in C9ORF72-mutated neurons. Moreover, we highlighted novel molecular pathways (nuclear and mitochondrial transports, vesicle trafficking, mitochondrial bioenergetics, glucose metabolism, ER-phagosome crosstalk and Slit/Robo signaling pathway) which might be further investigated as C9ORF72-specific pathogenetic mechanisms. Data are available via ProteomeXchange with the identifier PXD023866.The ocular surface is a gateway that contacts the outside and receives stimulation from the outside. The corneal innate immune system is composed of many types of cells, including epithelial cells, fibroblasts, natural killer cells, macrophages, neutrophils, dendritic cells, mast cells, basophils, eosinophils, mucin, and lysozyme. Neutrophil infiltration and degranulation occur on the ocular surface. Degranulation, neutrophil extracellular traps formation, called NETosis, and autophagy in neutrophils are involved in the pathogenesis of ocular surface diseases. It is necessary to understand the role of neutrophils on the ocular surface. Furthermore, there is a need for research on therapeutic agents targeting neutrophils and neutrophil extracellular trap formation for ocular surface diseases.The precise synthesis of fine-sized nanoparticles is critical for realizing the advantages of nanoparticles for various applications. We developed a technique for preparing finely controllable sizes of gold nanoparticles (Au NPs) on a silica template, using the seed-mediated growth and interval dropping methods. These Au NPs, embedded on silica nanospheres (SiO2@Au NPs), possess peroxidase-like activity as nanozymes and have several advantages over other nanoparticle-based nanozymes. We confirmed their peroxidase activity; in addition, factors affecting the activity were investigated by varying the reaction conditions, such as concentrations of tetramethyl benzidine and H2O2, pH, particle amount, reaction time, and termination time. We found that SiO2@Au NPs are highly stable under long-term storage and reusable for five cycles. Our study, therefore, provides a novel method for controlling the properties of nanoparticles and for developing nanoparticle-based nanozymes.Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and significantly impacts patients' lives, particularly in its severe forms. AD clinical presentation varies over the course of the disease, throughout different age groups, and across ethnicities. AD is characterized by a spectrum of clinical phenotypes as well as endotypes. Starting from the current description of AD pathogenesis, this review explores the rationale of approved AD therapies from emollients to biologicals and introduces novel promising drugs.Cancer still remains a leading cause of death despite improvements in diagnosis, drug discovery and therapy approach. Therefore, there is a strong need to improve methodologies as well as to increase the number of approaches available. Natural compounds of different origins (i.e., from fungi, plants, microbes, etc.) represent an interesting approach for fighting cancer. In particular, synergistic strategies may represent an intriguing approach, combining natural compounds with classic chemotherapeutic drugs to increase therapeutic efficacy and lower the required drug concentrations. In this review, we focus primarily on those natural compounds utilized in synergistic approached to treating cancer, with particular attention to those compounds that have gained the most research interest.Brassinazole-resistant (BZR) family genes encode plant-specific transcription factors (TFs), play essential roles in the regulation of plant growth and development, and have multiple stress-resistance functions. Nicotiana benthamiana is a model plant widely used in basic research. However, members of the BZR family in N. benthamiana have not been identified, and little is known about their function in abiotic stress. In this study, a total of 14 BZR members were identified in the N. selleck kinase inhibitor benthamiana genome, which could be divided into four groups according to a phylogenetic tree. NbBZRs have similar exon-intron structures and conserved motifs, and may be regulated by cis-acting elements such as STRE, TCA, and ARE, etc. Organ-specific expression analysis showed that NbBZR members have different and diverse expression patterns in different tissues, and most of the members are expressed in roots, stems, and leaves. The analysis of the expression patterns in response to different abiotic stresses showed that all the tested NbBZR members showed a significant down-regulation after drought treatment. Many NbBZR genes also responded in various ways to cold, heat and salt stress treatments. The results imply that NbBZRs have multiple functions related to stress resistance.A continuously increasing amount of research shows that oxytocin is involved in numerous central functions. Among the functions in which oxytocin is thought to be involved are those that play a role in social and sexual behaviors, and the involvement of central oxytocin in erectile function and sexual behavior was indeed one of the first to be discovered in laboratory animals in the 1980s. The first part of this review summarizes the results of studies done in laboratory animals that support a facilitatory role of oxytocin in male and female sexual behavior and reveal mechanisms through which this ancient neuropeptide participates in concert with other neurotransmitters and neuropeptides in this complex function, which is fundamental for the species reproduction. The second part summarizes the results of studies done mainly with intranasal oxytocin in men and women with the aim to translate the results found in laboratory animals to humans. Unexpectedly, the results of these studies do not appear to confirm the facilitatory role of oxytocin found in male and female sexual behavior in animals, both in men and women. Possible explanations for the failure of oxytocin to improve sexual behavior in men and women and strategies to attempt to overcome this impasse are considered.Despite the considerable advances in diagnostic methods in medicine, central nervous system (CNS) tumors, particularly the most common ones-gliomas-remain incurable, with similar incidence rates and mortality. A growing body of literature has revealed that degradation of the extracellular matrix by matrix metalloproteinases (MMPs) might be involved in the pathogenesis of CNS tumors. However, the subfamily of MMPs, known as disintegrin and metalloproteinase (ADAM) proteins are unique due to both adhesive and proteolytic activities. The objective of our review is to present the role of ADAMs in CNS tumors, particularly their involvement in the development of malignant gliomas. Moreover, we focus on the diagnostic and prognostic significance of selected ADAMs in patients with these neoplasms. It has been proven that ADAM12, ADAMTS4 and 5 are implicated in the proliferation and invasion of glioma cells. In addition, ADAM8 and ADAM19 are correlated with the invasive activity of glioma cells and unfavorable survival, while ADAM9, -10 and -17 are associated with tumor grade and histological type of gliomas and can be used as prognostic factors. In conclusion, several ADAMs might serve as potential diagnostic and prognostic biomarkers as well as therapeutic targets for malignant CNS tumors. However, future research on ADAMs biology should be performed to elucidate new strategies for tumor diagnosis and treatment of patients with these malignancies.MicroRNAs (miRNAs) participate in atrial remodeling and atrial fibrillation (AF) promotion. We determined the circulating miRNA profile in patients with AF and heart failure with reduced ejection fraction (HFrEF), and its potential role in promoting the arrhythmia. In plasma of 98 patients with HFrEF (49 with AF and 49 in sinus rhythm, SR), differential miRNA expression was determined by high-throughput microarray analysis followed by replication of selected candidates. Validated miRNAs were determined in human atrial samples, and potential arrhythmogenic mechanisms studied in HL-1 cells. Circulating miR-199a-5p and miR-22-5p were significantly increased in HFrEF patients with AF versus those with HFrEF in SR. Both miRNAs, but particularly miR-199a-5p, were increased in atrial samples of patients with AF. Overexpression of both miRNAs in HL-1 cells resulted in decreased protein levels of L-type Ca2+ channel, NCX and connexin-40, leading to lower basal intracellular Ca2+ levels, fewer inward currents, a moderate reduction in Ca2+ buffering post-caffeine exposure, and a deficient cell-to-cell communication. In conclusion, circulating miR-199a-5p and miR-22-5p are higher in HFrEF patients with AF, with similar findings in human atrial samples of AF patients. Cells exposed to both miRNAs exhibited altered Ca2+ handling and defective cell-to-cell communication, both findings being potential arrhythmogenic mechanisms.Rett syndrome (RTT) is a severe neurodevelopmental disorder that constitutes the second most common cause of intellectual disability in females worldwide. In the past few years, the advancements in genetic diagnosis brought by next generation sequencing (NGS), have made it possible to identify more than 90 causative genes for RTT and significantly overlapping phenotypes (RTT spectrum disorders). Therefore, the clinical entity known as RTT is evolving towards a spectrum of overlapping phenotypes with great genetic heterogeneity. Hence, simultaneous multiple gene testing and thorough phenotypic characterization are mandatory to achieve a fast and accurate genetic diagnosis. In this review, we revise the evolution of the diagnostic process of RTT spectrum disorders in the past decades, and we discuss the effectiveness of state-of-the-art genetic testing options, such as clinical exome sequencing and whole exome sequencing. Moreover, we introduce recent technological advancements that will very soon contribute to the increase in diagnostic yield in patients with RTT spectrum disorders. Techniques such as whole genome sequencing, integration of data from several "omics", and mosaicism assessment will provide the tools for the detection and interpretation of genomic variants that will not only increase the diagnostic yield but also widen knowledge about the pathophysiology of these disorders.