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ABSTRACTLeccinum scabrum (Bull.) Gray (Boletaceae) is an edible mycorrhizal species with potential application interest due to its food and medicinal properties. A field investigation carried out during summer in the Białowieża Primeval Forest, located along the border between Belarus and Poland allowed to collect samples for chemical composition analysis and antibacterial activity evaluation. Mushroom extracts were prepared with microwave-assisted as well as ultrasound-assisted extraction techniques (UAE and MAE). The analysis of a dry sample of L. scabrum showed a significant content of vitamins and minerals and also a remarkable content of carbohydrates, protein, dietary fibre, total sugars, total free amino acids, and polyunsaturated fatty acids. The antibacterial activity of L. scabrum aqueous extracts showed inhibitory activity against all tested bacteria. In general, MAE extract exhibits a higher inhibition activity against Listeria monocytogenes ATCC 19114. As regards the Minimum Inhibitory Concentration (MIC) values, the high antibacterial activity of MAE extract was detected for L. monocytogenes ATCC 19114 and Escherichia coli ATCC 25922. Regarding UAE, high antibacterial activity was detected for Salmonella enterica ATCC 13076 and L. monocytogenes ATCC 19114. Based on data hereby reported, L. scabrum is a culinary-medicinal mushroom with a promising potential use as a high-quality food and nutraceutical mycological resource.

This study introduces a novel mechanobiology assay, named “i-Rheo-optical assay”, that integrates rheology with optical microscopy for analysing the viscoelastic properties of multicellular spheroids. These spheroids serve as three-dimensional models resembling tissue structures. The innovative technique enables real-time observation and quantification of morphological responses to applied stress using a cost-effective microscope coverslip for constant compression force application. By bridging a knowledge gap in biophysical research, which has predominantly focused on the elastic properties while only minimally exploring the viscoelastic nature in multicellular systems, the i-Rheo-optical assay emerges as an effective tool. It facilitates the measurement of broadband viscoelastic compressional moduli in spheroids, here derived from cancer (PANC-1) and non-tumoral (NIH/3T3) cell lines during compression tests.This approach plays a crucial role in elucidating the mechanical properties of spheroids and holds potential for identifying biomarkers to discriminate between healthy tissues and their pathological counterparts. Offering comprehensive insights into the biomechanical behaviour of biological systems, i-Rheo-optical assay marks a significant advancement in tissue engineering, cancer research, and therapeutic development.

Type-2 diabetes affects an increasing percentage of the world’s population and its control through dietary management, involving the consumption of health-promoting foods or their derived supplements, is a common strategy. Several mushroom species have been demonstrated to be endowed with antidiabetic properties, resulting from their ability in improving insulin sensitivity and production, or inhibiting the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase. This study aimed to investigate for the first time the hypoglycemic properties of the edible mushroom Leccinum scabrum (Bull.) Gray. Mushroom extracts were prepared through the microwave-assisted extraction (MAE) technique using green solvents with different polarity degrees. The inhibition activity of all the obtained extracts on both α-glucosidase and α-amylase was evaluated and the highest activity was observed for the EtOAc extract which showed an IC50 value about 60-fold lower than the reference compound 1-deoxynojirimycin (DNJ) on α-glucosidase (0.42 ± 0.02 and 25.4 ± 0.6 µg/mL, respectively). As expected on the basis of the literature data concerning both α-glucosidase and α-amylase inhibition, a milder inhibition activity on pancreatic α-amylase was observed. Preliminary in vivo tests on Drosophila melanogaster carried out on the most active obtained extract (EtOAc) confirmed the in vitro observed hypoglycemic activity. Finally, the EtOAc extract metabolic profile was determined through GC-MS and HRMS analyses.

Nowadays, disruptive events pose significant threats to organizations, making resilience a critical focus. Evaluating supply chain resilience is essential to avoid escalating disruptions. However, the literature on this topic is fragmented, and the assessment of resilience remains an open gap due to the lack of a clear definition of the dimensions and elements for its evaluation. To fill this gap, this study integrates a systematic literature review (SLR) and a systematic literature network analysis (SLNA) to propose a MAturity MOdel for REsilient Supply Chains (MaMoReS). Through content analysis and stringent selection of 15 resilience maturity models (ResMMs) via SLR, along with an SLNA on 6,474 sources, this method defines dimensions and sub-dimensions. The proposed MaMoReS is framed around five levels and five dimensions: risk management, agility, flexibility and adaptability, redundancy and robustness, transparency and visibility, and collaboration and relationships. The MaMoReS is applied to two case studies, pinpointing the practicality of the MaMoReS for measuring the resilience maturity level of the two companies along with their dimensions and sub-dimensions scoring. Thus, the MaMoReS can be used as an assessment tool by supply chain managers and researchers to evaluate the resilience of a supply chain.

The freshwater environment is suitable for nontuberculous mycobacteria (NTMs) growth. Their high adaptability represents a considerable risk for sanitary water systems, which are a potential vector for NTMs transmission. This study investigated the occurrence of NTMs, such as Mycobacterium saskatchewanense, in hospital water systems to support the surveillance and control of potentially pathogenic NTMs. We analyzed 722 ultrapure dialysis fluid samples from Emilia Romagna Dialysis Services. Among these, 35 samples were found to be positive for M. saskatchewanense. The strains were characterized using whole-genome sequencing (WGS) and variability analysis was carried out along the whole M. saskatchewanense genome. This investigation revealed the exclusive presence of M. saskatchewanense in these dialysis machines, with low genetic variability among all strains (with a low number of different alleles:

Stress profoundly affects physical and mental health, particularly when experienced early in life. Early-life stress (ELS) encompasses adverse childhood experiences such as abuse, neglect, violence, or chronic poverty. These stressors can induce long-lasting changes in brain structure and function, impacting areas involved in emotion regulation, cognition, and stress response. Consequently, individuals exposed to high levels of ELS are at an increased risk for mental health disorders like depression, anxiety, and post-traumatic stress disorders, as well as physical health issues, including metabolic disorders, cardiovascular disease, and cancer. This review explores the biological and psychological consequences of early-life adversity paradigms in rodents, such as maternal separation or deprivation and limited bedding or nesting. The study of these experimental models have revealed that the organism’s response to ELS is complex, involving genetic and epigenetic mechanisms, and is associated with the dysregulation of physiological systems like the nervous, neuroendocrine, and immune systems, in a sex-dependent fashion. Understanding the impact of ELS is crucial for developing effective interventions and preventive strategies in humans exposed to stressful or traumatic experiences in childhood.

Ferulic acid (Fer) and geraniol (Ger) are natural compounds whose antioxidant and anti-inflammatory activity confer beneficial properties, such as antibacterial, anticancer, and neuroprotective effects. However, the short half-lives of these compounds impair their therapeutic activities after conventional administration. We propose, therefore, a new prodrug (Fer-Ger) obtained by a bio-catalyzed ester conjugation of Fer and Ger to enhance the loading of solid lipid microparticles (SLMs) designed as Fer-Ger delivery and targeting systems. SLMs were obtained by hot emulsion techniques without organic solvents. HPLC-UV analysis evidenced that Fer-Ger is hydrolyzed in human or rat whole blood and rat liver homogenates, with half-lives of 193.64 ± 20.93, 20.15 ± 0.75, and 3.94 ± 0.33 min, respectively, but not in rat brain homogenates. Studies on neuronal-differentiated mouse neuroblastoma N2a cells incubated with the reactive oxygen species (ROS) inductor H2O2 evidenced the Fer-Ger ability to prevent oxidative injury, despite the fact that it appears ROS-promoting. The amounts of Fer-Ger encapsulated in tristearin SLMs, obtained in the absence or presence of glucose, were 1.5 ± 0.1%, allowing the control of the prodrug release (glucose absence) or to sensibly enhance its water dissolution rate (glucose presence). These new “green” carriers can potentially prolong the beneficial effects of Fer and Ger or induce neuroprotection as nasal formulations.

As the most energy- and metabolite-consuming process, protein synthesis is under the control of several intrinsic and extrinsic factors that determine its fine-tuning to the cellular microenvironment. Consequently, variations in protein synthesis rates occur under various physiological and pathological conditions, enabling an adaptive response by the ce•ll. For example, global protein synthesis increases upon mitogenic factors to support biomass generation and cell proliferation, while exposure to low concentrations of oxygen or nutrients require translational repression and reprogramming to avoid energy depletion and cell death. To assess fluctuations in protein synthesis rates, radioactive isotopes or radiolabeled amino acids are often used. Although highly sensitive, these techniques involve the use of potentially toxic radioactive compounds and require specific materials and processes for the use and disposal of these molecules. The development of alternative, non-radioactive methods that can be easily and safely implemented in laboratories has therefore been encouraged to avoid handling radioactivity. In this context, the SUrface SEnsing of Translation (SUnSET) method, based on the classical western blot technique, was developed by Schmidt et al. in 2009. The SUnSET is nowadays recognized as a simple alternative to radioactive methods assessing protein synthesis rates.Key features• As a structural analogue of aminoacyl-transfer RNA, puromycin incorporates into the elongating peptide chain.• Detection of puromycin-labeled peptides by western blotting reflects translation rates without the need for radioactive isotopes.• The protocol described here for in vitro applications is derived from the SUnSET method originally published by Schmidt et al. (2009).

This research focuses on the target deconvolution of the natural compound myrianthic acid, a triterpenoid characterized by an ursane skeleton isolated from the roots of Myrianthus arboreus and from Oenothera maritima Nutt. (Onagraceae), using MS-based chemical proteomic techniques. Application of drug affinity responsive target stability (DARTS) and targeted-limited proteolysis coupled to mass spectrometry (t-LiP-MS) led to the identification of the enzyme fatty acid synthase (FAS) as an interesting macromolecular counterpart of myrianthic acid. This result, confirmed by comparison with the natural ursolic acid, was thoroughly investigated and validated in silico by molecular docking, which gave a precise picture of the interactions in the MA/FAS complex. Moreover, biological assays showcased the inhibitory activity of myrianthic acid against the FAS enzyme, most likely related to its antiproliferative activity towards tumor cells. Given the significance of FAS in specific pathologies, especially cancer, the myrianthic acid structural moieties could serve as a promising reference point to start the potential development of innovative approaches in therapy.

Four common processing pipelines tested on two Voxel-based Morphometry (VBM) datasets yield considerable variations in results, raising issues on the interpretability and robustness of VBM results.

This research investigates the visible upconversion luminescence which is induced by multiphoton absorption of soft glass fiber defects. The study of this phenomenon has thus far been restricted to standard silica fibers. We observed the emission of green and cyan light as a consequence of fiber material ionization. We investigate both the commercial ZBLAN step index and in-house-made tellurite nanostructured graded-index fibers. For the latter, the analysis of the luminescence signal permits us to determine the core and cladding refractive index difference. Upconversion luminescence is a powerful tool for characterizing soft glass fibers and a promising platform for innovative photonic technologies and mid-IR applications.

Cells and extracts derived from adipose tissue are gaining increasing attention not only in plastic surgery and for aesthetic purposes but also in regenerative medicine. The ability of hyaluronan (HA) to support human adipose stromal cell (hASC) viability and differentiation has been investigated. However, the compatibility of adipose tissue with HA-based formulation in terms of biophysical and rheological properties has not been fully addressed, although it is a key feature for tissue integration and in vivo performance. In this study, the biophysical and biochemical properties of highly concentrated (45 mg/mL) high/low-molecular-weight HA hybrid cooperative complex were assessed with a further focus on the potential application in adipose tissue augmentation/regeneration. Specifically, HA hybrid complex rheological behavior was observed in combination with different adipose tissue ratios, and hyaluronidase-catalyzed degradation was compared to that of a high-molecular-weight HA (HHA). Moreover, the HA hybrid complex’s ability to induce in vitro hASCs differentiation towards adipose phenotype was evaluated in comparison to HHA, performing Oil Red O staining and analyzing gene/protein expression of PPAR-γ, adiponectin, and leptin. Both treatments supported hASCs differentiation, with the HA hybrid complex showing better results. These outcomes may open new frontiers in regenerative medicine, supporting the injection of highly concentrated hybrid formulations in fat compartments, eventually enhancing residing staminal cell differentiation and improving cell/growth factor persistence towards tissue regeneration districts.

Artemetin is a valuable 5-hydroxy-3,6,7,3′,4′-pentamethoxyflavone present in many different medicinal plants with very good oral bioavailability and drug-likeness values, owing to numerous bioactivities, such as anti-inflammatory and anti-cancer ones. Here, a multi-disciplinary plan has been settled and applied for identifying the artemetin target(s) to inspect its mechanism of action, based on drug affinity-responsive target stability and targeted limited proteolysis. Both approaches point to the disclosure of filamins A and B as direct artemetin targets in HeLa cell lysates, also giving detailed insights into the ligand/protein-binding sites. Interestingly, also 8-prenyl-artemetin, which is an artemetin more permeable semisynthetic analog, directly interacts with filamins A and B. Both compounds alter filamin conformation in living HeLa cells with an effect on cytoskeleton disassembly and on the disorganization of the F-actin filaments. Both the natural compound and its derivative are able to block cell migration, expectantly acting on tumor metastasis occurrence and development.

Background: Diabetic retinopathy (DR) is a neurovascular disease, characterized by a deficiency of brain-derived neurotrophic factor (BDNF), a regulator of autophagy. Beta-hydroxybutyrate (BHB), previously reported as a protective agent in DR, has been associated with BDNF promotion. Here, we investigated whether systemic BHB affects the retinal levels of BDNF and local autophagy in diabetic mice with retinopathy; Methods: C57BL/6J mice were administered with intraperitoneal (i.p.) streptozotocin (STZ) (75 mg/kg) injection to develop diabetes. After 2 weeks, they received i.p. injections of BHB (25–50–100 mg/kg) twice a week for 10 weeks. Retinal samples were collected in order to perform immunofluorescence, Western blotting, and ELISA analysis; Results: BHB 50 mg/kg and 100 mg/kg significantly improved retinal BDNF levels (p < 0.01) in diabetic mice. This improvement was negatively associated with autophagosome–lysosome formations (marked by LC3B and ATG14) and to higher levels of connexin 43 (p < 0.01), a marker of cell integrity. Moreover, BHB administration significantly reduced M1 microglial activation and autophagy (p < 0.01); Conclusions: The systemic administration of BHB in mice with DR improves the retinal levels of BDNF, with the consequent reduction of the abnormal microglial autophagy. This leads to retinal cell safety through connexin 43 restoration.

During the SARS-CoV-2 vaccination campaign, people with CF (pwCF) were considered a clinically vulnerable population. However, data on the immunogenicity of anti-SARS-CoV-2 vaccines in pwCF are lacking. We conducted a prospective study enrolling all patients aged > 12 and who were followed-up in our CF center and received two doses of the BNT162b2 vaccine in the period of March–October 2021. Blood samples were taken from them for the quantification of antibodies to the SARS-CoV-2 spike protein receptor binding domain immediately before receiving the first dose and 3 and 6 months after the second dose. We enrolled 143 patients (median age: 21 years, range: 13–38), 16 of whom had had a previous infection. Geometric mean antibody titer (GMT) 3 months after vaccination was 1355 U/mL (95% CI: 1165–1575) and decreased to 954 U/mL (95% CI: 819–1111) after 6 months (p < 0.0001). GMT was higher among previously infected patients as compared to those naïve to SARS-CoV-2 (6707 vs. 1119 U/mL at 3 months and 4299 vs. 796 U/mL at 6 months, p < 0.0001) with no significant differences in the rate of decline over time (p = 0.135). All pwCF mounted an antibody response after two doses of the BNT162b2 vaccine, which waned at 6 months from vaccination. Age ≥ 30 years and the use of inhaled corticosteroids were associated with a lower humoral response. Between the second and the third doses, nine episodes of vaccine breakthrough infections were observed.

The post-COVID-19 syndrome may affect patients after the COVID-19 post-acute phase. In particular, the 69% of patients reported persistent fatigue at the discharge. To date, no clear data are available regarding the most effective rehabilitative approaches for the treatment of this condition. Thus, this systematic review aimed to evaluate the rehabilitation treatment’s efficacy on fatigue in post-COVID-19 patients. We systematically searched PubMed, Scopus, and Web of Science databases to find longitudinal study designs presenting: post-COVID-19 patients as participants; a rehabilitative approach aimed to reduce post-COVID-19 syndrome as intervention; and fatigue intensity assessed through an evaluation tool that quantified the perceived exertion (i.e., fatigue severity scale, FSS; Borg Scale (BS); Borg Category Ratio 10, CR10; Checklist Individual Strength (CIS) fatigue scale; FACIT (Functional Assessment of Chronic Illness Therapy) fatigue scale). The present systematic review protocol was registered on PROSPERO (registration number CRD42021284058). Out of 704 articles, 6 studies were included. Nearly all patients showed COVID-19-related fatigue, and after the rehabilitation treatment, only 17% of subjects reported the persistency of symptoms. The overall effect size reported a −1.40 decrease in Borg Category Ratio 10 with a SE of 0.05 and a 95% CI between −1.50 and −1.30 (p < 0.001). The present systematic review and meta-analysis underlines the rehabilitation role in the fatigue reduction in patients affected by post-COVID-19 syndrome.

The research interest in the field of inorganic medicinal chemistry had a large increase after the serendipitous discovery of the cytotoxic activity of cisplatin by Rosenberg at the end of 1960s [...]

Mediastinal lymphadenopathy and auto-antibodies are clinical phenomena during ischemic heart failure pointing to an autoimmune response against the heart. T and B cells have been convincingly demonstrated to be activated after myocardial infarction, a prerequisite for the generation of mature auto-antibodies. Yet, little is known about the immunoglobulin isotype repertoire thus pathological potential of anti-heart auto-antibodies during heart failure. We obtained human myocardial tissue from ischemic heart failure patients and induced experimental MI in rats. We found that anti-heart autoimmunity persists during heart failure. Rat mediastinal lymph nodes are enlarged and contain active secondary follicles with mature isotype-switched IgG2a B cells. Mature IgG2a auto-antibodies specific for cardiac antigens are present in rat heart failure serum, and IgG and complement C3 deposits are evident in heart failure tissue of both rats and human patients. Previously established myocardial inflammation, and the herein provided proof of B cell maturation in lymph nodes and myocardial deposition of mature auto-antibodies, provide all the hallmark signs of an established autoimmune response in chronic heart failure.

Summary: TRAP1 is the mitochondrial paralog of the heat shock protein 90 (HSP90) chaperone family. Its activity as an energy metabolism regulator has important implications in cancer, neurodegeneration, and ischemia. Selective inhibitors of TRAP1 could inform on its mechanisms of action and set the stage for targeted drug development, but their identification was hampered by the similarity among active sites in HSP90 homologs. We use a dynamics-based approach to identify a TRAP1 allosteric pocket distal to its active site that can host drug-like molecules, and we select small molecules with optimal stereochemical features to target the pocket. These leads inhibit TRAP1, but not HSP90, ATPase activity and revert TRAP1-dependent downregulation of succinate dehydrogenase activity in cancer cells and in zebrafish larvae. TRAP1 inhibitors are not toxic per se, but they abolish tumorigenic growth of neoplastic cells. Our results indicate that exploiting conformational dynamics can expand the chemical space of chaperone antagonists to TRAP1-specific inhibitors with wide therapeutic opportunities. : The molecular chaperone TRAP1 regulates energy metabolism, and its activity is relevant in cancer and degenerative diseases. Here, Sanchez-Martin et al. identify highly selective allosteric inhibitors of TRAP1. These compounds revert biochemical and pro-neoplastic effects of TRAP1 and could both enlighten its mode of action and disclose novel therapeutic strategies. Keywords: chaperone inhibitors, anticancer compound, molecular dynamics, allosteric ligands, TRAP1, HSP90, mitochondria, mitochondrial biology, zebrafish, cancer cells, neurofibroma

Autosomal recessive osteopetrosis (ARO) is a rare inherited disorder leading to increased bone density with impairment in bone resorption. Among the genes responsible for ARO, the TCIRG1 gene, coding for the a3 subunit of the osteoclast proton pump, is mutated in more than 50% of the cases, increasing the importance of TCIRG1-iPSCs as disease model. We generated 3 iPSC clones derived from Peripheral Blood Mononuclear Cells (PBMCs) of a patient carrying the heterozygous mutations p.Y512X and c.2236 + 1G > A. A Sendai virus-based vector was used and the iPSCs were characterized for genetic identity to parental cells, genomic integrity, pluripotency, and differentiation ability.

Fibroblasts from a patient with Aicardi Goutières Syndrome (AGS) carrying a compound heterozygous mutation in TREX1, were reprogrammed into induced pluripotent stem cells (iPSCs) to establish isogenic clonal stem cell lines: UNIBSi006-A, UNIBSi006-B, and UNIBSi006-C. Cells were transduced using the episomal Sendai viral vectors, containing human OCT4, SOX2, c-MYC and KLF4 transcription factors. The transgene-free iPSC lines showed normal karyotype, expressed pluripotent markers and displayed in vitro differentiation potential toward cells of the three embryonic germ layers.

Background Conventional methods used to identify BRCA1 and BRCA2 germline mutations in hereditary cancers, such as Sanger sequencing/multiplex ligation-dependent probe amplification (MLPA), are time-consuming and expensive, due to the large size of the genes. The recent introduction of next-generation sequencing (NGS) benchtop platforms offered a powerful alternative for mutation detection, dramatically improving the speed and the efficiency of DNA testing. Here we tested the performance of the Ion Torrent PGM platform with the Ion AmpliSeq BRCA1 and BRCA2 Panel in our clinical routine of breast/ovarian hereditary cancer syndrome assessment. Methods We first tested the NGS approach in a cohort of 11 patients (training set) who had previously undergone genetic diagnosis in our laboratory by conventional methods. Then, we applied the optimized pipeline to the consecutive cohort of 136 uncharacterized probands (validation set). Results By minimal adjustments in the analytical pipeline of Torrent Suite Software we obtained a 100% concordance with Sanger results regarding the identification of single nucleotide alterations, insertions, and deletions with the exception of three large genomic rearrangements (LGRs) contained in the training set. The optimized pipeline applied to the validation set (VS), identified pathogenic and polymorphic variants, including a novel BRCA2 pathogenic variant at exon 3, 100% of which were confirmed by Sanger in their correct zygosity status. To identify LGRs, all negative samples of the VS were subjected to MLPA analysis. Discussion Our experience strongly supports that the Ion Torrent PGM technology in BRCA1 and BRCA2 germline variant identification, combined with MLPA analysis, is highly sensitive, easy to use, faster, and cheaper than traditional (Sanger sequencing/MLPA) approaches.

We aimed to evaluate the effects of aerobic exercise training (4 days) and metformin exposure on acute glucose intolerance after dexamethasone treatment in rats. Forty-two adult male Wistar rats (8 weeks old) were divided randomly into four groups: sedentary control (SCT), sedentary dexamethasone-treated (SDX), training dexamethasone-treated (DPE), and dexamethasone and metformin treated group (DMT). Glucose tolerance tests and in situ liver perfusion were undertaken on fasting rats to obtain glucose profiles. The DPE group displayed a significant decrease in glucose values compared with the SDX group. Average glucose levels in the DPE group did not differ from those of the DMT group, so we suggest that exercise training corrects dexamethasone-induced glucose intolerance and improves glucose profiles in a similar manner to that observed with metformin. These data suggest that exercise may prevent the development of glucose intolerance induced by dexamethasone in rats to a similar magnitude to that observed after metformin treatment.

Albino Grifola frondosa (Dicks.) Gray “maitake” mushrooms (described as G. albicans Imazeki and then placed in synonymy with G. frondosa) are particularly rare, and the few pertinent records are not treated in scientific publications. A field investigation carried out in Sicily (Italy) led to the collection of an unusual white Grifola specimen at the base of a living tree of Quercus pubescens Willd. s.l. The outcome of sequencing the internal transcribed spacer (ITS) region of nuclear ribosomal DNA (nrDNA) indicated that it belongs to G. frondosa and provided an insight to the phylogenetic relationships within the genus. The results of nutritional composition analysis showed that the albino basidioma possesses relatively high contents of Ca, Fe, K, and Cu and is rather low in Na when compared with literature data on edible mushrooms. Vitamin (B1, B2, B3, B5, B9, and D2) contents ranged from 0.15 to 3.89 mg per 100 g of mushroom dry weight. The cold-water extract of this specimen was effective at inhibiting the growth of Staphylococcus epidermidis ATCC 12228 and Pseudomonas aeruginosa ATCC 15442 at the maximum screening concentration of 50% v/v. In addition, the extract slowed down the ability of Staphylococcus aureus ATCC 43300 to form biofilms. According to data hereby reported, the albino G. frondosa is a culinary-medicinal mushroom with a promising exploitation potential.

Toxic and heavy metals are considered harmful derivatives of industrial activities; they are not biodegradable and their accumulation in living organisms can become lethal. Among other heavy and toxic metals, chromium is considered hazardous, especially in the hexavalent (Cr6+) form. Numerous established studies show that exposure to Cr6+ via drinking water leads to elevated chromium levels in tissues, which may result in various forms of cancer. The purpose of this research is to synthesize magnetite/zeolite-X composite particles for the adsorption and magnetic removal of Cr6+ ions from aqueous solutions. Synthesis and characterization of such composite nanomaterials, along with an initial experimental evaluation of Cr6+ removal from water-based solution, are presented. Results show that zeolite-X is a very promising zeolite form, that when bound to magnetic nanoparticles can be used to trap and magnetically remove toxic ions from aqueous solutions.

Inflammation is strictly associated with cancer and plays a key role in tumor development and progression. Several epidemiological studies have demonstrated that inflammation can predispose to tumors, therefore targeting inflammation and the molecules involved in the inflammatory process could represent a good strategy for cancer prevention and therapy. In the past, several clinical studies have demonstrated that many anti-inflammatory agents, including non-steroidal anti-inflammatory drugs (NSAIDs), are able to interfere with the tumor microenvironment by reducing cell migration and increasing apoptosis and chemo-sensitivity. This review focuses on the link between inflammation and cancer by describing the anti-inflammatory agents used in cancer therapy, and their mechanisms of action, emphasizing the use of novel anti-inflammatory agents with significant anticancer activity.

Appropriate in utero growth is essential for offspring development and is a critical contributor to long-term health. Fetal growth is largely dictated by the availability of nutrients in maternal circulation and the ability of these nutrients to be transported into fetal circulation via the placenta. Substrate flux across placental gradients is dependent on the accessibility and activity of nutrient-specific transporters. Changes in the expression and activity of these transporters is implicated in cases of restricted and excessive fetal growth, and may represent a control mechanism by which fetal growth rate attempts to match availability of nutrients in maternal circulation. This review provides an overview of placenta nutrient transport with an emphasis on macro-nutrient transporters. It highlights the changes in expression and activity of these transporters associated with common pregnancy pathologies, including intrauterine growth restriction, macrosomia, diabetes and obesity, as well as the potential impact of maternal diet. Molecular signaling pathways linking maternal nutrient availability and placenta nutrient transport are discussed. How sexual dimorphism affects fetal growth strategies and the placenta’s response to an altered intrauterine environment is considered. Further knowledge in this area may be the first step in the development of targeted interventions to help optimize fetal growth.

The simultaneous expression of the hunchback gene in the numerous nuclei of the developing fly embryo gives us a unique opportunity to study how transcription is regulated in living organisms. A recently developed MS2-MCP technique for imaging nascent messenger RNA in living Drosophila embryos allows us to quantify the dynamics of the developmental transcription process. The initial measurement of the morphogens by the hunchback promoter takes place during very short cell cycles, not only giving each nucleus little time for a precise readout, but also resulting in short time traces of transcription. Additionally, the relationship between the measured signal and the promoter state depends on the molecular design of the reporting probe. We develop an analysis approach based on tailor made autocorrelation functions that overcomes the short trace problems and quantifies the dynamics of transcription initiation. Based on live imaging data, we identify signatures of bursty transcription initiation from the hunchback promoter. We show that the precision of the expression of the hunchback gene to measure its position along the anterior-posterior axis is low both at the boundary and in the anterior even at cycle 13, suggesting additional post-transcriptional averaging mechanisms to provide the precision observed in fixed embryos.

Platinum(II) complexes with different cinnamic acid derivatives as ligands were investigated for their ability to inhibit the aggregation process of amyloid systems derived from Aβ, Yeast Prion Protein Sup35p and the C-terminal domain of nucleophosmin 1. Thioflavin T binding assays and circular dichroism data indicate that these compounds strongly inhibit the aggregation of investigated peptides exhibiting IC50 values in the micromolar range. MS analysis confirms the formation of adducts between peptides and Pt(II) complexes that are also able to reduce amyloid cytotoxicity in human SH-SY5Y neuroblastoma cells. Overall data suggests that bidentate ligands based on β-hydroxy dithiocinnamic esters can be used to develop platinum or platinoid compounds with anti-amyloid aggregation properties.

Stable five-coordinate Pt(II) complexes have been highlighted as a promising and original platform for the development of new cytotoxic drugs. Their interaction with proteins has been scarcely studied. Here, the reactivity of the five-coordinate Pt(II) compound [Pt(I)(Me) (dmphen)(olefin)] (Me = methyl, dmphen = 2,9-dimethyl-1,10-phenanthroline, olefin = dimethylfumarate) with the model proteins hen egg white lysozyme (HEWL) and bovine pancreatic ribonuclease (RNase A) has been investigated by X-ray crystallography and electrospray ionization mass spectrometry. The X-ray structures of the adducts of RNase A and HEWL with [Pt(I)(Me)(dmphen)(olefin)] are not of very high quality, but overall data indicate that, upon reaction with RNase A, the compound coordinates the side chain of His105 upon releasing the iodide ligand, but retains the pentacoordination. On the contrary, upon reaction with HEWL, the trigonal bi-pyramidal Pt geometry is lost, the iodide and the olefin ligands are released, and the metal center coordinates the side chain of His15 probably adopting a nearly square-planar geometry. This work underlines the importance of the combined use of crystallographic and mass spectrometry techniques to characterize, in detail, the protein⁻metallodrug recognition process. Our findings also suggest that five-coordinate Pt(II) complexes can act either retaining their uncommon structure or functioning as prodrugs, i.e., releasing square-planar platinum complexes as bioactive species.

Larrea divaricata Cav. is widely distributed in Argentina. Aqueous extract, of its leaves, has documented antitumoral and immunomodulatory activities. In this study, the antioxidant activity of aqueous extract and a component, nordihydroguaiaretic acid was determined and compared using different assays. Both the aqueous extract and nordihydroguaiaretic acid exhibited antioxidant activity. However, results show that it is very likely that compounds other than nordihydroguaiaretic acid could be involved in the antioxidant activity of the extract. Since nordihydroguaiaretic acid is nephrotoxic and hepatotoxic agent, it is important to direct efforts toward the potential use of low-nordihydroguaiaretic acid L. divaricata extracts as antioxidant in foods.

A team from UF/IFAS has developed an app for optimizing your home irrigation system using real-time weather data from the Florida Automated Weather Network (FAWN). Learn more in this 5-page fact sheet written by K.W. Migliaccio, N.A. Dobbs, W.R. Lusher, J. Fan, M.D. Dukes, K.T. Morgan, and B. Ferraro, and published by the UF Department of Agricultural and Biological Engineering, March 2012.

A team from UF/IFAS has developed an app for optimizing your home irrigation system using real-time weather data from the Florida Automated Weather Network (FAWN). Learn more in this 5-page fact sheet written by K.W. Migliaccio, N.A. Dobbs, W.R. Lusher, J. Fan, M.D. Dukes, K.T. Morgan, and B. Ferraro, and published by the UF Department of Agricultural and Biological Engineering, March 2012.

A team from UF/IFAS has developed an app for optimizing your home irrigation system using real-time weather data from the Florida Automated Weather Network (FAWN). Learn more in this 5-page fact sheet written by K.W. Migliaccio, N.A. Dobbs, W.R. Lusher, J. Fan, M.D. Dukes, K.T. Morgan, and B. Ferraro, and published by the UF Department of Agricultural and Biological Engineering, March 2012.

Fish assemblages associated with extractive platforms were surveyed, for the first time, using traditional fishing surveys (bottom gill net) and an underwater visual census (UVC) technique in order to test the effectiveness and to identify strengths and weaknesses of both methods. The study was carried out during three seasons at two offshore gas platforms (Eleonora and Squalo C) located in the central Adriatic Sea. Both methods recorded a similar number of fish species although with only eight species in common, thus supplying complementary information and a good estimate of the total fish species richness (39) associated with these gas platforms. The use of innovative techniques, such as UVC, to explore the inner part of the platforms, allowed the censusing of several cryptobenthic species, mostly Blennidae (8 species), never recorded during previous studies. Even if both methods were able to detect temporal variability, only the UVC technique was able to highlight spatial changes between platforms, demonstrating their high efficiency regarding the quality of the scientific information supplied. The innovative method of studying biodiversity presented in this study appears to be highly reproducible and suitable for monitoring fish diversity in artificial and very complex habitats like gas platforms.

Abstract Background Microarray experiments enable simultaneous measurement of the expression levels of virtually all transcripts present in cells, thereby providing a ‘molecular picture’ of the cell state. On the other hand, the genomic responses to a pharmacological or hormonal stimulus are dynamic molecular processes, where time influences gene activity and expression. The potential use of the statistical analysis of microarray data in time series has not been fully exploited so far, due to the fact that only few methods are available which take into proper account temporal relationships between samples. Results We compared here four different methods to analyze data derived from a time course mRNA expression profiling experiment which consisted in the study of the effects of estrogen on hormone-responsive human breast cancer cells. Gene expression was monitored with the innovative Illumina BeadArray platform, which includes an average of 30-40 replicates for each probe sequence randomly distributed on the chip surface. We present and discuss the results obtained by applying to these datasets different statistical methods for serial gene expression analysis. The influence of the normalization algorithm applied on data and of different parameter or threshold choices for the selection of differentially expressed transcripts has also been evaluated. In most cases, the selection was found fairly robust with respect to changes in parameters and type of normalization. We then identified which genes showed an expression profile significantly affected by the hormonal treatment over time. The final list of differentially expressed genes underwent cluster analysis of functional type, to identify groups of genes with similar regulation dynamics. Conclusions Several methods for processing time series gene expression data are presented, including evaluation of benefits and drawbacks of the different methods applied. The resulting protocol for data analysis was applied to characterization of the gene expression changes induced by estrogen in human breast cancer ZR-75.1 cells over an entire cell cycle.

Se estudiaron las comunidades ícticas asociadas con plataformas extractivas mediante dos técnicas de censos visuales submarinos: transectos y conteos de puntos móviles. Los datos se tomaron a cuatro profundidades en tres diferentes plataformas situadas en el Mar Jónico (Crotone, Italia). Se registraron un total de 25 especies de peces pertenecientes a 12 familias. Se observaron diferencias significativas entre ambos métodos de muestreo y las profundidades en cuanto a la estructura de la comunidad íctica, la riqueza de especies y la abundancia de peces. El promedio de peces registrado con el método de transectos siempre fue mayor que el registrado mediante puntos móviles, mientras que lo contrario sucedió para las abundancias medias. Las especies gregarias como Boops boops, Chromis chromis, Anthias anthias y Oblada melanura fueron las que más contribuyeron a las diferencias en la estructura poblacional. Ambas técnicas permitieron observar especies que no son comúnmente capturadas con artes de pesca. Cuando se utilizan las dos técnicas, éstas proporcionan información complementaria con respecto a las comunidades ícticas estrictamente asociadas con las estructuras de las plataformas. Fish assemblages associated with offshore platforms were surveyed using two underwater visual census techniques: strip transects and mobile point counts. Data were collected from four depth ranges at three platforms off Crotone, Italy (Ionian Sea). A total of 25 fish species belonging to 12 families were recorded for the three platforms. Significant differences between sampling methods and depth were observed in the fish assemblage structure, species richness and fish abundance. The mean number of species recorded with the strip transect method was always greater than that obtained with mobile point counts, whilst the opposite pattern was observed for mean abundances. Gregarious species such as Boops boops, Chromis chromis, Anthias anthias and Oblada melanura were responsible for most of the differences in the assemblage structure. According to our results, both methods allowed us to observe species that are not usually caught by means of fishing gear. When both census techniques are used, they provide complementary information about the fish assemblages strictly associated with the platform structures.

Tatridin A (TatA) is a germacrane sesquiterpenoid containing one E-double bond and one Z-double bond in its 10-membered ring, which is fused to a 3-methylene-dihydrofuran-2-one moiety. Tatridin A bioactivity has been poorly investigated despite its interesting chemical structure. Here, a functional proteomic platform was adapted to disclose its most reliable targets in leukemia monocytic cells, and phosphoglycerate kinases were recognized as the most affine enzymes. Through a combination of limited proteolysis and molecular docking, it has been discovered that tatridin A interacts with the active domains of phosphoglycerate kinase 1, altering its hinge region, and it can be accountable for tatridin A inhibition potency on enzyme activity. A more detailed tatridin A biological profile showed that it is also fully active against gastric cancer cells, downregulating the mRNA levels of chemokine receptor 4 and β-catenin and inhibiting the invasiveness of living KATO III cells as a direct consequence of phosphoglycerate kinase 1 antagonism.

Abstract Background Huge amounts of molecular interaction data are continuously produced and stored in public databases. Although many bioinformatics tools have been proposed in the literature for their analysis, based on their modeling through different types of biological networks, several problems still remain unsolved when the problem turns on a large scale. Results We propose DIAMIN, that is, a high-level software library to facilitate the development of applications for the efficient analysis of large-scale molecular interaction networks. DIAMIN relies on distributed computing, and it is implemented in Java upon the framework Apache Spark. It delivers a set of functionalities implementing different tasks on an abstract representation of very large graphs, providing a built-in support for methods and algorithms commonly used to analyze these networks. DIAMIN has been tested on data retrieved from two of the most used molecular interactions databases, resulting to be highly efficient and scalable. As shown by different provided examples, DIAMIN can be exploited by users without any distributed programming experience, in order to perform various types of data analysis, and to implement new algorithms based on its primitives. Conclusions The proposed DIAMIN has been proved to be successful in allowing users to solve specific biological problems that can be modeled relying on biological networks, by using its functionalities. The software is freely available and this will hopefully allow its rapid diffusion through the scientific community, to solve both specific data analysis and more complex tasks.

Abstract Considered the economic engine of many countries, the coffee culture represents an important component of the agricultural chain in Brazil. The growing values of commercialization, planting areas, and crop productivity require the acquisition of quality seedlings, which must receive adequate nutritional support through efficient fertilizers. Slow and controlled-release fertilizers, such as organominerals, gain prominence when it comes to increasing efficiency in the use of phosphorus, as well as plant growth-promoting bacteria (PGPB) with phosphate solubilizing characteristics. This study aimed to evaluate the effect of different sources of mineral and organomineral fertilizers, inoculated and non-inoculated with PGPB on the quality parameters of coffee seedlings. In general, the P sources used in the experiment positively interfered with the development of coffee seedlings. This proves that there is a need for nutritional supplementation for the good development of the seedlings. Among the sources used, the organomineral in granulated form showed better performance in coffee seedlings' growth and physiological parameters, proving to be a viable alternative to commonly used fertilizers. The addition of PGPB showed a significant advantage for seedling quality variables.

Abstract Background In vertebrate cells, the Golgi functional subunits, mini-stacks, are linked into a tri-dimensional network. How this “ribbon” architecture relates to Golgi functions remains unclear. Are all connections between mini-stacks equal? Is the local structure of the ribbon of functional importance? These are difficult questions to address, without a quantifiable readout of the output of ribbon-embedded mini-stacks. Endothelial cells produce secretory granules, the Weibel-Palade bodies (WPB), whose von Willebrand Factor (VWF) cargo is central to hemostasis. The Golgi apparatus controls WPB size at both mini-stack and ribbon levels. Mini-stack dimensions delimit the size of VWF "boluses” whilst the ribbon architecture allows their linear co-packaging, thereby generating WPBs of different lengths. This Golgi/WPB size relationship suits mathematical analysis. Results WPB lengths were quantized as multiples of the bolus size and mathematical modeling simulated the effects of different Golgi ribbon organizations on WPB size, to be compared with the ground truth of experimental data. An initial simple model, with the Golgi as a single long ribbon composed of linearly interlinked mini-stacks, was refined to a collection of mini-ribbons and then to a mixture of mini-stack dimers plus long ribbon segments. Complementing these models with cell culture experiments led to novel findings. Firstly, one-bolus sized WPBs are secreted faster than larger secretory granules. Secondly, microtubule depolymerization unlinks the Golgi into equal proportions of mini-stack monomers and dimers. Kinetics of binding/unbinding of mini-stack monomers underpinning the presence of stable dimers was then simulated. Assuming that stable mini-stack dimers and monomers persist within the ribbon resulted in a final model that predicts a “breathing” arrangement of the Golgi, where monomer and dimer mini-stacks within longer structures undergo continuous linking/unlinking, consistent with experimentally observed WPB size distributions. Conclusions Hypothetical Golgi organizations were validated against a quantifiable secretory output. The best-fitting Golgi model, accounting for stable mini-stack dimers, is consistent with a highly dynamic ribbon structure, capable of rapid rearrangement. Our modeling exercise therefore predicts that at the fine-grained level the Golgi ribbon is more complex than generally thought. Future experiments will confirm whether such a ribbon organization is endothelial-specific or a general feature of vertebrate cells.

Lung cancer frequently affects patients with Chronic Obstructive Pulmonary Disease (COPD). Cigarette smoke (CS) fosters cancer progression by increasing oxidative stress and by modulating epithelial-mesenchymal transition (EMT) processes in cancer cells. Formoterol (FO), a long-acting β2-agonist widely used for the treatment of COPD, exerts antioxidant activities. This study explored in a lung adenocarcinoma cell line (A549) whether FO counteracted the effects of cigarette smoke extract (CSE) relative to oxidative stress, inflammation, EMT processes, and cell migration and proliferation. A549 was stimulated with CSE and FO, ROS were evaluated by flow-cytometry and by nanostructured electrochemical sensor, EMT markers were evaluated by flow-cytometry and Real-Time PCR, IL-8 was evaluated by ELISA, cell migration was assessed by scratch and phalloidin test, and cell proliferation was assessed by clonogenic assay. CSE significantly increased the production of ROS, IL-8 release, cell migration and proliferation, and SNAIL1 expression but significantly decreased E-cadherin expression. FO reverted all these phenomena in CSE-stimulated A549 cells. The present study provides intriguing evidence that FO may exert anti-cancer effects by reverting oxidative stress, inflammation, and EMT markers induced by CS. These findings must be validated in future clinical studies to support FO as a valuable add-on treatment for lung cancer management.

Nitric oxide (NO) is produced within the airways and released with exhalation. Nasal NO (nNO) can be measured in a non-invasive way, with different devices and techniques according to the age and cooperation of the patients. Here, we conducted a narrative review of the literature to examine the relationship between nNO and some respiratory diseases with a particular focus on primary ciliary dyskinesia (PCD). A total of 115 papers were assessed, and 50 were eventually included in the review. nNO in PCD is low (below 77 nL/min), and its measurement has a clear diagnostic value when evaluated in a clinically suggestive phenotype. Many studies have evaluated the role of NO as a molecular mediator as well as the association between nNO values and genotype or ciliary function. As far as other respiratory diseases are concerned, nNO is low in chronic rhinosinusitis and cystic fibrosis, while increased values have been found in allergic rhinitis. Nonetheless, the role in the diagnosis and prognosis of these conditions has not been fully clarified.

We investigated SARS-CoV-2 variants circulating, from November 2020 to March 2022, among military and civilian personnel at an Air Force airport in Italy in order to classify viral isolates in a potential hotspot for virus spread. Positive samples were subjected to Next-Generation Sequencing (NGS) of the whole viral genome and Sanger sequencing of the spike coding region. Phylogenetic analysis classified viral isolates and traced their evolutionary relationships. Clusters were identified using 70% cut-off. Sequencing methods yielded comparable results in terms of variant classification. In 2020 and 2021, we identified several variants, including B.1.258 (4/67), B.1.177 (9/67), Alpha (B.1.1.7, 9/67), Gamma (P.1.1, 4/67), and Delta (4/67). In 2022, only Omicron and its sub-lineage variants were observed (37/67). SARS-CoV-2 isolates were screened to detect naturally occurring resistance in genomic regions, the target of new therapies, comparing them to the Wuhan Hu-1 reference strain. Interestingly, 2/30 non-Omicron isolates carried the G15S 3CLpro substitution responsible for reduced susceptibility to protease inhibitors. On the other hand, Omicron isolates carried unusual substitutions A1803V, D1809N, and A949T on PLpro, and the D216N on 3CLpro. Finally, the P323L substitution on RdRp coding regions was not associated with the mutational pattern related to polymerase inhibitor resistance. This study highlights the importance of continuous genomic surveillance to monitor SARS-CoV-2 evolution in the general population, as well as in restricted communities.

Fungal biodiversity is still mostly unknown and their presence in particular ecosystems such as freshwater habitats is often underestimated. The ecological role that these fungi play in freshwater environments mainly concerns their activity as decomposers of litter and plant material. At present, it is estimated that 3870 species belong to the ecological group of freshwater fungi (13 phyla and 45 classes). In this survey, we provide an overview of the Italian freshwater fungal diversity on the basis of the field and literature data. In the literature, data on freshwater fungi are fragmentary and not updated, focusing mainly on northern Italy where the most important lakes and rivers are present, while data from central and southern Italy (including Sicily and Sardinia) are almost completely ineffective. In particular, Ascomycota are reported in only 14 publications, most of which concern the freshwater environments of Lombardia, Piemonte, and Veneto. Only one publication explores the biodiversity of freshwater Basidiomycota in the wetlands of the Cansiglio forest (Veneto). The field observation allowed for us to identify 38 species of Basidiomycota growing in riparian forest of Italy. However, the number of fungi in freshwater habitats of Italy is strongly underestimated and many species are still completely unknown.

Beer is one of the oldest and most popular alcoholic beverages and is currently consumed worldwide. The various components used in the brewing process have a physiological impact on the consumer and current research aims to improve its technological and functional properties through the addition of natural compounds (plants or mushrooms). In this work, the addition of two different amounts (5 and 10 g/L) of Pleurotus eryngii var. eryngii in powder form added at different production stages (PRE and POST alcoholic fermentation) showed the improvement in yeast viability during the alcoholic fermentation, increased the alcoholic content, and improved the sensorial profile. Regarding the organoleptic profile in the experimental samples, cocoa/chocolate and mushroom aromas were found and the samples PRE10 and POST5 received the best ratings with respect to all evaluated parameters.

For their easy and high-yield recombinant production, their high stability in a wide range of physico-chemical conditions and their characteristic hollow structure, ferritins (Fts) are considered useful scaffolds to encapsulate bioactive molecules. Notably, for the absence of immunogenicity and the selective interaction with tumor cells, the nanocages constituted by the heavy chain of the human variant of ferritin (hHFt) are optimal candidates for the delivery of anti-cancer drugs. hHFt nanocages can be disassembled and reassembled in vitro to allow the loading of cargo molecules, however the currently available protocols present some relevant drawbacks. Indeed, protein disassembly is achieved by exposure to extreme pH (either acidic or alkaline), followed by incubation at neutral pH to allow reassembly, but the final protein recovery and homogeneity are not satisfactory. Moreover, the exposure to extreme pH may affect the structure of the molecule to be loaded. In this paper, we report an alternative, efficient and reproducible procedure to reversibly disassemble hHFt under mild pH conditions. We demonstrate that a small amount of sodium dodecyl sulfate (SDS) is sufficient to disassemble the nanocage, which quantitatively reassembles upon SDS removal. Electron microscopy and X-ray crystallography show that the reassembled protein is identical to the untreated one. The newly developed procedure was used to encapsulate two small molecules. When compared to the existing disassembly/reassembly procedures, our approach can be applied in a wide range of pH values and temperatures, is compatible with a larger number of cargos and allows a higher protein recovery.

In order to examine the role of the circadian clock driver Brain and Muscle ARNT-Like 1 (Bmal1) in alcohol consumption, de Zavalia et al assess the effects of (Bmal1) deletion in the mouse striatum on alcohol drinking behavior. They show that striatal Bmal1 and downstream effects on Period Circadian Regulator 2 (Per2) play a sex-dependent role on alcohol consumption propensity.

Maturity models (MMs) are strategic tools used to assess and improve the current state of processes, objects, or people, with the goal of achieving continuous performance enhancement. While MMs are applied in various fields, their scope, design, and application criteria within Supply Chain Management and Logistics (SCML) lack comprehensive studies. This article aims to address this gap through a systematic literature review. The review analyzes 137 relevant articles using both bibliometric and content analysis techniques. The bibliometric analysis identifies major contributions, popular journals, and the classification and evolution of key keywords. The content analysis focuses on critical criteria related to the scope, design, and application of MMs. The findings reveal a growing emphasis on models assessing Industry 4.0 readiness and sustainability principles. However, several gaps are identified, including limited attention to optimizing and integrating logistic processes, underutilized and unvalidated MMs, and the absence of comprehensive improvement guidelines. Based on these trends and research gaps, this study proposes five recommendations for future developments that benefit both academics and practitioners. These recommendations aim to address the identified limitations and provide guidance for comprehensive and effective improvement strategies.

Sex is a biological variable that can reflect clinical outcomes in terms of quality of life, therapy effectiveness, responsiveness and/or toxicity. Sphingosine-1-phosphate (S1P) is a lipidic mediator whose activity can be influenced by sex. To evaluate whether the S1P axis underlies sex ‘instructions’ in the lung during physiological and oncological lung conditions, sphingosine and S1P were quantified in the blood of healthy (H) volunteers, lung adenocarcinoma (ADK) and squamous cell carcinoma (SCC) patients of both sexes. S1P receptors and their metabolic enzymes were evaluated in the tissues. Circulating levels of S1P were similar among H female and male subjects and female SCC patients. Instead, male and female ADK patients had lower circulating S1P levels. S1P receptor 3 (S1PR3) was physiologically expressed in the lung, but it was overexpressed in male SCC, and female and male ADK, but not in female SCC patients, who showed a significantly reduced ceramide synthase 1 (CERS1) mRNA and an overexpression of the ceramidase (ASAH1) precursor in lung tumor tissues, compared to male SCC and both male and female ADK patients. These findings highlighted sex differences in S1P rheostat in pathological conditions, but not in physiological conditions, identifying S1P as a prognostic mediator depending on lung cancer histotype.