Cavity-Based Discovery of New Fatty Acid Photodecarboxylases.

Light-dependent fatty acid photodecarboxylases (FAPs) hold significant potential for biotechnology, due to their capability to produce alka(e)nes directly from the corresponding (un)saturated natural fatty acids requiring light as the only reagent. This study expands the family of FAPs through cavity-based enzyme discovery methods. Thirty enzyme candidates with potential photodecarboxylation activity were identified by matching the cavities of four related template structures against the Protein Data Bank's flavoproteins, a library of proteins identified via the Foldseek Search Server, and homology models of sequences resulting from BLAST.

Paternal microbiome perturbations impact offspring fitness.

The gut microbiota operates at the interface of host-environment interactions to influence human homoeostasis and metabolic networks. Environmental factors that unbalance gut microbial ecosystems can therefore shape physiological and disease-associated responses across somatic tissues. However, the systemic impact of the gut microbiome on the germline-and consequently on the F offspring it gives rise to-is unexplored.

Innovative Techniques for Infection Control and Surveillance in Hospital Settings and Long-Term Care Facilities: A Scoping Review.

Healthcare-associated infections (HAIs) pose significant challenges in healthcare systems, with preventable surveillance playing a crucial role. Traditional surveillance, although effective, is resource-intensive. The development of new technologies, such as artificial intelligence (AI), can support traditional surveillance in analysing an increasing amount of health data or meeting patient needs.

An Integrative Transcriptomics and Proteomics Approach to Identify Putative Genes Underlying Fruit Ripening in Tomato near Isogenic Lines with Long Shelf Life.

The elucidation of the ripening pathways of climacteric fruits helps to reduce postharvest losses and improve fruit quality. Here, we report an integrative study on tomato ripening for two near-isogenic lines (NIL115 and NIL080) with LA0722 introgressions. A comprehensive analysis using phenotyping, molecular, transcript, and protein data were performed.

Discovery of RC-752, a Novel Sigma-1 Receptor Antagonist with Antinociceptive Activity: A Promising Tool for Fighting Neuropathic Pain.

Neuropathic pain (NP) is a chronic condition resulting from damaged pain-signaling pathways. It is a debilitating disorder that affects up to 10% of the world's population. Although opioid analgesics are effective in reducing pain, they present severe risks; so, there is a pressing need for non-opioid pain-relieving drugs.

BRAT1-related disorders: phenotypic spectrum and phenotype-genotype correlations from 97 patients.

BRAT1 biallelic variants are associated with rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL), and neurodevelopmental disorder associating cerebellar atrophy with or without seizures syndrome (NEDCAS). To date, forty individuals have been reported in the literature. We collected clinical and molecular data from 57 additional cases allowing us to study a large cohort of 97 individuals and draw phenotype-genotype correlations.

From Nature to Synthetic Compounds: Novel 1(N),2,3 Trisubstituted-5-oxopyrrolidines Targeting Multiple Myeloma Cells.

The insurgence of drug resistance in treating Multiple Myeloma (MM) still represents a major hamper in finding effective treatments, although over the past decades new classes of drugs, such as proteasome inhibitors and immunomodulatory drugs, have been discovered. Recently, our research team, within a Nature-Aided Drug Discovery project, isolated from L. calyces the secondary metabolite called Hib-ester which possesses antiproliferative properties against human multiple myeloma RPMI 8226 cells, reduces migration and cell invasion and inhibits proteasome without neurotoxic effects.

Genotypes and phenotypes heterogeneity in PIK3CA-related overgrowth spectrum and overlapping conditions: 150 novel patients and systematic review of 1007 patients with PIK3CA pathogenetic variants.

Background: Postzygotic activating variants cause several phenotypes within the -related overgrowth spectrum (PROS). Variant strength, mosaicism level, specific tissue involvement and overlapping disorders are responsible for disease heterogeneity. We explored these factors in 150 novel patients and in an expanded cohort of 1007 mutated patients, analysing our new data with previous literature to give a comprehensive picture.

DNA methylation episignature testing improves molecular diagnosis of Mendelian chromatinopathies.

Purpose: Chromatinopathies include more than 50 disorders caused by disease-causing variants of various components of chromatin structure and function. Many of these disorders exhibit unique genome-wide DNA methylation profiles, known as episignatures. In this study, the methylation profile of a large cohort of individuals with chromatinopathies was analyzed for episignature detection.

The effect of co-payments on the take-up of prenatal tests.

Noninvasive prenatal screening tests help identify genetic disorders in a fetus, but their take-up remains low in several countries. Using a regression discontinuity design, we test the causal effect of a policy that eliminated co-payments for noninvasive screening tests in Italy. We identify the treatment effects by a discontinuity in women's eligibility for a free test based on their conception date.

Novel Frameshift Mutation in a Patient Affected by a Syndromic Form of Neurodevelopmental Disorder.

The cohesin complex is a large evolutionary conserved functional unit which plays an essential role in DNA repair and replication, chromosome segregation and gene expression. It consists of four core proteins, SMC1A, SMC3, RAD21, and STAG1/2, and by proteins regulating the interaction between the complex and the chromosomes. Mutations in the genes coding for these proteins have been demonstrated to cause multisystem developmental disorders known as "cohesinopathies".

Chd8 regulates X chromosome inactivation in mouse through fine-tuning control of Xist expression.

Female mammals achieve dosage compensation by inactivating one of their two X chromosomes during development, a process entirely dependent on Xist, an X-linked long non-coding RNA (lncRNA). At the onset of X chromosome inactivation (XCI), Xist is up-regulated and spreads along the future inactive X chromosome. Contextually, it recruits repressive histone and DNA modifiers that transcriptionally silence the X chromosome.

Mechanisms underlying the hormetic effect of conjugated linoleic acid: Focus on Nrf2, mitochondria and NADPH oxidases.

Nuclear factor erythroid 2-related factor2 (Nrf2) is a redox-sensitive transcription factor. Its activation by low dietary intake of ligands leads to antioxidant effects (eustress), while pro-oxidant effects (oxidative distress) may be associated with high doses. NADPH oxidases (NOXs) and the mitochondrial electron transport chain are the main sources of intracellular ROS, but their involvement in the biphasic/hormetic activity elicited by Nrf2 ligands is not fully understood.

Improving clinical interpretation of five KRIT1 and PDCD10 intronic variants.

Cerebral cavernous malformation (CCM) is a vascular malformation of the central nervous system which may occur sporadically or segregate within families due to heterozygous variants in KRIT1/CCM1, MGC4607/CCM2 or PDCD10/CCM3. Intronic variants are not uncommon in familial CCM, but their clinical interpretation is often hampered by insufficient data supporting in silico predictions. Here, the mRNA analysis for two intronic unpublished variants (KRIT1 c.

Whole Exome Sequencing Reveals a Novel In-Frame Deletion in a Boy with Global Developmental Delay, Absent Speech, Dysmorphic Features, and Cerebral Anomalies.

Neurodevelopmental disorders (NDDs) are a group of highly prevalent, clinically and genetically heterogeneous pediatric disorders comprising, according to the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-V), intellectual disability, developmental delay, autism spectrum disorders, and other neurological and cognitive disorders manifesting in the developmental age. To date, more than 1000 genes have been implicated in the etiopathogenesis of NNDs. Among them, (OMIM # 607270) encodes a protein involved in neural migration and neuritogenesis, and causes NNDs with different molecular mechanisms including copy number variations, single or multiple exonic deletion and single nucleotide variants.

Modulation of Human Sperm Mitochondrial Respiration Efficiency by Plant Polyphenols.

Plant bioactives, such as polyphenols, can differentially affect (positively or negatively) sperm quality, depending on their concentration. These molecules have been proposed as natural scavengers of reactive oxygen species (ROS) for male infertility treatment. However, few data are available about their effects on the molecular mechanisms related to sperm quality and, in particular, to sperm mitochondrial function.

Herbicides glyphosate and glufosinate ammonium negatively affect human sperm mitochondria respiration efficiency.

The widespread cultivation of genetically modified organisms (GMOs) led to a widespread use of selective herbicides to which GMOs are resistant, thus increasing the concern about human exposure to them. Glyphosate (GLY) and glufosinate ammonium (GA), the active principles of the main formulations, have been investigated for their effects on human health, mainly cancer and reproductive toxicity. However, little is known about their effects on the molecular mechanisms related to sperm quality.

Exploring the RC-106 Chemical Space: Design and Synthesis of Novel ()-1-(3-Arylbut-2-en-1-yl)-4-(Substituted) Piperazine Derivatives as Potential Anticancer Agents.

Despite the fact that significant advances in treatment of common cancers have been achieved over the years, orphan tumors still represent an important unmet medical need. Due to their complex multifactorial origin and limited number of cases, such pathologies often have very limited treatment options and poor prognosis. In the search for new anticancer agents, our group recently identified , a Sigma receptor modulator endowed with proteasome inhibition activity.

Application of response surface methodology (RSM) for the optimization of supercritical CO extraction of oil from patè olive cake: Yield, content of bioactive molecules and biological effects in vivo.

The two-phase technology for olive oil extraction generates large amounts of patè olive cake (POC), a by-product that is rich in bioactive health-promoting compounds. Here, response surface methodology (RSM) was used to maximize supercritical-CO oil extraction from POC, while minimizing operative temperature, pressure and time. Under the optimal parameters (40.

BOPC1 Enantiomers Preparation and HuR Interaction Study. From Molecular Modeling to a Curious DEEP-STD NMR Application.

The Hu family of RNA-binding proteins plays a crucial role in post-transcriptional processes; indeed, Hu-RNA complexes are involved in various dysfunctions (i.e., inflammation, neurodegeneration, and cancer) and have been recently proposed as promising therapeutic targets.

Customised next-generation sequencing multigene panel to screen a large cohort of individuals with chromatin-related disorder.

Background: The regulation of the chromatin state by epigenetic mechanisms plays a central role in gene expression, cell function, and maintenance of cell identity. Hereditary disorders of chromatin regulation are a group of conditions caused by abnormalities of the various components of the epigenetic machinery, namely writers, erasers, readers, and chromatin remodelers. Although neurological dysfunction is almost ubiquitous in these disorders, the constellation of additional features characterizing many of these genes and the emerging clinical overlap among them indicate the existence of a community of syndromes.

Centrifugation Force and Time Alter CASA Parameters and Oxidative Status of Cryopreserved Stallion Sperm.

Conventional sperm selection techniques used in ARTs rely on centrifugation steps. To date, the different studies reported on the effects of centrifugation on stallion sperm motility provided contrasting results and do not include effects on mitochondrial functionality and different oxidative parameters. The effects of different centrifugation protocols (300 ×g for 5', 300 ×g for 10', 1500 ×g for 5' and 1500 ×g for 10' vs no centrifugation) on motility and oxidative status in cryopreserved stallion sperm, were analyzed.

Crosstalk between mitochondrial metabolism and oxidoreductive homeostasis: a new perspective for understanding the effects of bioactive dietary compounds.

Mitochondria play an important role in a number of fundamental cellular processes, including energy production, biosynthetic pathways and cellular oxidoreductive homeostasis (redox status), and their dysfunction can lead to numerous pathophysiological consequences. As the biochemical mechanisms orchestrating mitochondrial metabolism and redox homeostasis are functionally linked, mitochondria have been identified as a potential therapeutic target. Consequently, considerable effort has been made to evaluate the efficacy of natural compounds that modulate mitochondrial function.

Prunus Mahaleb Fruit Extract Prevents Chemically Induced Colitis and Enhances Mitochondrial Oxidative Metabolism via the Activation of the Nrf2 Pathway.

Scope: Polyphenols exhibit their antioxidant activity downstream the activation of the nuclear factor erythroid 2-related factor 2 pathway (Nrf2), but the connection between lipid metabolism and the Nrf2 pathway is still unknown. Flavonoid-rich concentrated extract from Prunus mahaleb (mahaleb concentrated fruit extract; MCFE) may act on oxido-reductive homeostasis and hepatic lipid metabolism via Nrf2.

Methods & Results: MCFE ability to enhance the activity of Nrf2-mediated antioxidant/detoxifying enzymes is investigated in liver and colon of BALB/c mice.