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Atrial natriuretic peptide (ANP), a cardiac hormone involved in the regulation of water/sodium balance and blood pressure, is also secreted by endothelial cells, where it exerts protective effects in response to stress. Autophagy is an intracellular self-renewal process involved in the degradation of dysfunctional cytoplasmic elements. ANP was recently reported to act as an extracellular regulator of cardiac autophagy. However, its role in the regulation of endothelial autophagy has never been investigated. Here, we tested the effects of ANP in the regulation of autophagy in human umbilical vein endothelial cells (HUVECs). We found that ANP rapidly increases autophagy and autophagic flux at physiological concentrations through its predominant pathway, mediated by natriuretic peptide receptor type A (NPR-A) and protein kinase G (PKG). We further observed that ANP is rapidly secreted by HUVEC under stress conditions, where it mediates stress-induced autophagy through autocrine and paracrine mechanisms. Finally, we found that the protective effects of ANP in response to high-salt loading or tumor necrosis factor (TNF)-α are blunted by concomitant inhibition of autophagy. Overall, our results suggest that ANP acts as an endogenous autophagy activator in endothelial cells. The autophagy mechanism mediates the protective endothelial effects exerted by ANP., Competing Interests: Declaration of competing interest None to disclose., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Micronutrients such as vitamins are transferred from lower to higher trophic levels, but no general ecological concept describes the factors regulating this process. Here, we investigated thiamin (thiamine, vitamin B1), which is an example of a metabolically important water-soluble micronutrient. Thiamin is produced by organisms such as bacteria and phytoplankton, and all consumers, such as zooplankton and fish, rely on a continuous intake of thiamin through their diet and possibly from de novo-synthesized thiamin by gut microbiota. A deficiency in thiamin negatively affects reproduction in fish and bird populations worldwide. The aim of this study was to quantify thiamin transfer in a planktonic food web in response to thiamin and/or nutrient addition, using an outdoor mesocosm system (an approximately 1.9 m3 bag submerged in sea water). These estimates were then compared with literature data on thiamin concentrations at different trophic levels. The results showed that thiamin was rapidly taken up by phytoplankton in both the ambient and nutrient-amended treatments. However, large differences in thiamin concentrations in phytoplankton did not lead to any significant changes in community composition or abundance. Nitrogen addition led to changes in the abundance and community composition of picoplankton and phytoplankton but there were no additional major effects of thiamin addition. Differences in thiamin concentrations in phytoplankton were not detected at the next trophic level in zooplankton. Although the concentrations did not change, a greater abundance of some zooplankton taxa were developed in the thiamin treatments. Comparing the mesocosm results with literature data demonstrated a gradual reduction in thiamin concentrations along the food chain, with six percent of the concentration in producers occurring in top consumers (i.e., piscivorous fish). Overall, these observations illustrate the concept of trophic dilution of micronutrients where concentrations decrease along the food web from phytoplankton via zooplankton and planktivorous fish to piscivorous fish., Competing Interests: No competing interests., (Copyright: © 2024 Hylander et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Animal movements are a key factor in the spread of pathogens. Consequently, network analysis of animal movements is a well-developed and well-studied field. The relationships between animals facilitate the diffusion of infectious agents and, in particular, shared environments and close interactions can facilitate cross-species transmission. Cattle are often the focus of these studies since they are among the most widely distributed and traded species globally. This remains true for Italy as well, but with an important additional consideration. Indeed, another important productive reality in the peninsula is buffalo farming. These farms have an interesting characteristic: approximately two-thirds of them also rear cattle. This coexistence between cattle and buffalo could have an impact on the diffusion of pathogens. Given that buffalo farms are often overlooked in the literature, the primary goal of this work is to investigate the potential consequences of omitting buffalo from cattle network analyses. To investigate this impact, we will focus on Q fever, a disease that can infect both species and is present on the Italian territory and for which the impact of the buffalo population has not been thoroughly studied, and simulate its spread to the farms of both species through compartmental models. Our analysis reveals that despite the significant difference in network sizes, the unique characteristic of Italian buffalo farms makes the buffalo network essential for a comprehensive understanding of bovine disease dynamics in Italy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zoppi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Lung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) constituting approximately 84 % of all lung cancer cases. The role of inflammation in the initiation and progression of NSCLC tumors has been the focus of extensive research. Among the various inflammatory mediators, prostaglandin E2 (PGE2) plays a pivotal role in promoting the aggressiveness of epithelial tumors through multiple mechanisms, including the stimulation of growth, evasion of apoptosis, invasion, and induction of angiogenesis. The Extracellular signal-Regulated Kinase 5 (ERK5), the last discovered member among conventional mitogen-activated protein kinases (MAPK), is implicated in cancer-associated inflammation. In this study, we explored whether ERK5 is involved in the process of tumorigenesis induced by PGE2. Using A549 and PC9 NSCLC cell lines, we found that PGE2 triggers the activation of ERK5 via the EP1 receptor. Moreover, both genetic and pharmacological inhibition of ERK5 reduced PGE2-induced proliferation, migration, invasion and stemness of A549 and PC9 cells, indicating that ERK5 plays a critical role in PGE2-induced tumorigenesis. In summary, our study underscores the pivotal role of the PGE2/EP1/ERK5 axis in driving the malignancy of NSCLC cells in vitro. Targeting this axis holds promise as a potential avenue for developing novel therapeutic strategies aimed at controlling the advancement of NSCLC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Our study presents a novel enantioselective route for the synthesis of 1,2,3,4-tetrahydroquinolines via a chiral phosphoric acid-catalyzed three-component Povarov reaction, employing phenolic dienes as dienophiles. This approach produces a diverse array of 2,3,4-trisubstituted tetrahydroquinolines, each featuring a styryl group at position 4, in high yields with excellent regio-, diastereo-, and enantioselectivities (>95:5 dr and up to >99% ee).

Radiomics is an innovative field in Personalized Medicine to help medical specialists in diagnosis and prognosis. Mainly, the application of Radiomics to medical images requires the definition and delimitation of the Region Of Interest (ROI) on the medical image to extract radiomic features. The aim of this preliminary study is to define an approach that automatically detects the specific areas indicative of a particular disease and examines them to minimize diagnostic errors associated with false positives and false negatives. This approach aims to create a nxn grid on the DICOM image sequence and each cell in the matrix is associated with a region from which radiomic features can be extracted. The proposed procedure uses the Model Checking technique and produces as output the medical diagnosis of the patient, i.e., whether the patient under analysis is affected or not by a specific disease. Furthermore, the matrix-based method also localizes where appears the disease marks. To evaluate the performance of the proposed methodology, a case study on COVID-19 disease is used. Both results on disease identification and localization seem very promising. Furthermore, this proposed approach yields better results compared to methods based on the extraction of features using the whole image as a single ROI, as evidenced by improvements in Accuracy and especially Recall. Our approach supports the advancement of knowledge, interoperability and trust in the software tool, fostering collaboration among doctors, staff and Radiomics., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Antonella Santone reports financial support was provided by Ministry of Education and Merit and by Ministry of University and Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Drinking water (DW) production treatments can be affected by climate change, in particular intense rainfall events, having an impact on the availability and quality of the water source. The current study proposes a methodology for the evaluation of the costs of the different treatment steps for surface water (SW) and groundwater (GW), through the analysis and quantification of the main cost items. It provides the details to count for strong variations in the key quality parameters of inlet water following severe rainfalls (namely turbidity, iron, manganese, and E. coli). This methodology is then applied to a large drinking water treatment plant (DWTP) in Italy, which treats both SW, around 70 %, and GW, around 30%. It discusses the overall DW production costs (from 7.60 c€/m 3 to 10.43 c€/m 3 ) during the period 2019-2021 and analyzes the contributions of the different treatment steps in water and sludge trains. Then it focuses on the effects on the treatments of significant variations in SW turbidity (up to 1863 NTU) due to intense rainfalls, and on the daily costs of DW with respect to the average (baseline) costs evaluated on the annual basis. It emerges that, when SW has low turbidity levels, the energy-based steps have the biggest contribution on the costs (final pumping 22 % for SW and 10 % for GW, withdrawal 15 % and 14 %, respectively), whereas at very high turbidity levels, sludge greatly increases, and its treatment and disposal costs become significant (up to 14 % and 50 %). Efforts are being made to adopt the best strategies for the management of DWTPs in these adverse conditions, with the aim to guarantee potable water and optimize water production costs. A mitigation measure consists of increasing GW withdrawal up to the authorized flow rate, thus reducing SW withdrawal. In this context, the study is completed by discussing the potential upgrading of the DWTP by only treating GW withdrawn from riverbank filtration. The DW production cost would be 7.76 c€/m 3 , which is lower than that seen for the same year (2021) with the current plant configuration (8.32 c€/m 3 )., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Acrylamide determination is important to state its quantity in baked food preventing any potential carcinogenic effects. Matrix solid-phase dispersion (MSPD) extraction is an extraction procedure based on a homogenization phase between a solid sample and a solid dispersing material to break sample increasing analyte extraction yield, often used for acrylamide determination. The addition of a green deep eutectic solvent (DES) during the MSPD homogenization phase improves the analyte extraction, giving the possibility to reduce the amount of organic solvent used. In this work, a miniaturized MSPD extraction assisted by a DES was developed to determine acrylamide in bread, using high-performance liquid chromatography coupled with mass spectrometry detection. The optimized procedure provides 1:1 (w/w) matrix-to-dispersing material ratio, 2 mL of methanol as extraction solvent, and 50 μL of choline chloride-glycerol DES added during the homogenization phase. Method validation ensured good results with minimum recoveries of 90%, high precision with a maximum intra-day error of 4%, and inter-day error of 6%. Limit of detection and limit of quantification resulted to be 16 μg/kg and 35 μg/kg, respectively. This miniaturized extraction procedure represents a good alternative to those reported in the literature, guaranteeing great performance and respecting green chemistry principles., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Maladaptive cardiac hypertrophy contributes to the development of heart failure (HF). The oxidoreductase Selenoprotein T (SELENOT) emerged as a key regulator during rat cardiogenesis and acute cardiac protection. However, its action in chronic settings of cardiac dysfunction is not understood. Here, we investigated the role of SELENOT in the pathophysiology of HF: (i) by designing a small peptide (PSELT), recapitulating SELENOT activity via the redox site, and assessed its beneficial action in a preclinical model of HF [aged spontaneously hypertensive heart failure (SHHF) rats] and against isoproterenol (ISO)-induced hypertrophy in rat ventricular H9c2 and adult human AC16 cardiomyocytes; (ii) by evaluating the SELENOT intra-cardiomyocyte production and secretion under hypertrophied stimulation. Results showed that PSELT attenuated systemic inflammation, lipopolysaccharide (LPS)-induced macrophage M1 polarization, myocardial injury, and the severe ultrastructural alterations, while counteracting key mediators of cardiac fibrosis, aging, and DNA damage and restoring desmin downregulation and SELENOT upregulation in the failing hearts. In the hemodynamic assessment, PSELT improved the contractile impairment at baseline and following ischemia/reperfusion injury, and reduced infarct size in normal and failing hearts. At cellular level, PSELT counteracted ISO-mediated hypertrophy and ultrastructural alterations through its redox motif, while mitigating ISO-triggered SELENOT intracellular production and secretion, a phenomenon that presumably reflects the extent of cell damage. Altogether, these results indicate that SELENOT could represent a novel sensor of hypertrophied cardiomyocytes and a potential PSELT-based new therapeutic approach in myocardial hypertrophy and HF., (© 2024. The Author(s).)

Growing global use of heat-not-burn cigarettes (HNBC) prompts investigation. Prior studies assessed HNBC's effects on cardiovascular health, revealing heightened oxidative stress, platelet activation, and endothelial dysfunction. However, limited understanding exists regarding passive smoking's impact on children exposed to HNBC. This study aims to assess levels of oxidative stress, endothelial and platelet function among children exposed to passive smoke from HNBC, traditional tobacco (TT) cigarettes and unexposed subjects. Seventy-eight children (2-18 years) were divided into three groups: HNBC passive smokers (n = 26), TT cigarette exposed (n = 26), and control (CNT) group (n = 26, unexposed). Oxidative stress was evaluated by serum NADPH oxidase-2 (NOX2) activity, assessed by soluble Nox2-derived peptide (sNOX2-dp), isoprostanes, hydrogen peroxide (H 2 O 2 ) production, hydrogen break-down activity (HBA) and NO bioavailability. Endothelial function was assessed by brachial flow-mediated dilation (FMD). Platelet function was evaluated by soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin) and thrombus formation by T-TAS analysis. Passive smoking-exposed children (both HNBC and TT) exhibited significantly increased serum sNOX2-dp, isoprostanes, H2O2, sCD40L sP-selectin and thrombus formation versus controls. Conversely, exposed children displayed reduced brachial FMD and serum NO bioavailability. No significant differences were found between children exposed to passive smoking of HNBC vs TT. Multivariable regression linked sNOX2 (standardized coefficient β: 0.284; SE: 0.040; p = 0.01) and H 2 O 2 (standardized coefficient β: 0.243; SE: 0.0; p = 0.02) as independent predictors of FMD, and isoprostanes (standardized coefficient β:0.388; SE: 0.022; p < 0.001) and serum cotinine (standardized coefficient β:0.270; SE: 0.048; p = 0.01) with sNOX2-dp levels. Exposure to HNBC smoke heightened oxidative stress, endothelial dysfunction, platelet activation, and thrombus formation in children. Findings suggest avenues for interventions to curb childhood passive smoking exposure., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lorenzo Loffredo reports financial support was provided by University of Rome La Sapienza. Lorenzo Loffredo reports a relationship with University of Rome La Sapienza that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Oil and gas industries in the Northern Atlantic Ocean have gradually moved closer to the Arctic areas, a process expected to be further facilitated by sea ice withdrawal caused by global warming. Copepods of the genus Calanus hold a key position in these cold-water food webs, providing an important energetic link between primary production and higher trophic levels. Due to their ecological importance, there is a concern about how accidental oil spills and produced water discharges may impact cold-water copepods. In this review, we summarize the current knowledge of the toxicity of petroleum on North Atlantic and Arctic Calanus copepods. We also review how recent development of high-quality transcriptomes from RNA-sequencing of copepods have identified genes regulating key biological processes, like molting, diapause and reproduction in Calanus copepods, to suggest linkages between exposure, molecular mechanisms and effects on higher levels of biological organization. We found that the available ecotoxicity threshold data for these copepods provide valuable information about their sensitivity to acute petrogenic exposures; however, there is still insufficient knowledge regarding underlying mechanisms of toxicity and the potential for long-term implications of relevance for copepod ecology and phenology. Copepod transcriptomics has expanded our understanding of how key biological processes are regulated in cold-water copepods. These advances can improve our understanding of how pollutants affect biological processes, and thus provide the basis for new knowledge frameworks spanning the effect continuum from molecular initiating events to adverse effects of regulatory relevance. Such efforts, guided by concepts such as adverse outcome pathways (AOPs), enable standardized and transparent characterization and evaluation of knowledge and identifies research gaps and priorities. This review suggests enhancing mechanistic understanding of exposure-effect relationships to better understand and link biomarker responses to adverse effects to improve risk assessments assessing ecological effects of pollutant mixtures, like crude oil, in Arctic areas., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Adenosine deaminase (ADA) deficiency leads to severe combined immunodeficiency (SCID). Previous clinical trials showed that autologous CD34 + cell gene therapy (GT) following busulfan reduced-intensity conditioning is a promising therapeutic approach for ADA-SCID, but long-term data are warranted. Here we report an analysis on long-term safety and efficacy data of 43 patients with ADA-SCID who received retroviral ex vivo bone marrow-derived hematopoietic stem cell GT. Twenty-two individuals (median follow-up 15.4 years) were treated in the context of clinical development or named patient program. Nineteen patients were treated post-marketing authorization (median follow-up 3.2 years), and two additional patients received mobilized peripheral blood CD34 + cell GT. At data cutoff, all 43 patients were alive, with a median follow-up of 5.0 years (interquartile range 2.4-15.4) and 2 years intervention-free survival (no need for long-term enzyme replacement therapy or allogeneic hematopoietic stem cell transplantation) of 88% (95% confidence interval 78.7-98.4%). Most adverse events/reactions were related to disease background, busulfan conditioning or immune reconstitution; the safety profile of the real world experience was in line with premarketing cohort. One patient from the named patient program developed a T cell leukemia related to treatment 4.7 years after GT and is currently in remission. Long-term persistence of multilineage gene-corrected cells, metabolic detoxification, immune reconstitution and decreased infection rates were observed. Estimated mixed-effects models showed that higher dose of CD34 + cells infused and younger age at GT affected positively the plateau of CD3 + transduced cells, lymphocytes and CD4 + CD45RA + naive T cells, whereas the cell dose positively influenced the final plateau of CD15 + transduced cells. These long-term data suggest that the risk-benefit of GT in ADA remains favorable and warrant for continuing long-term safety monitoring. Clinical trial registration: NCT00598481 , NCT03478670 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Introduction: Delayed discharge represents the difficulty in proceeding with discharge of patients who do not have any further benefit from prolonged stay. A quota of this problem is related to organizational issues. In the Lazio region in Italy, a macro service re-organization in on the way, with a network of hospital and territorial centers engaged in structuring in- and out- of hospital patient pathways, with a special focus on intermediate care structures. Purpose of this study is to quantify the burden of delayed discharge on a single hospital structure, in order to estimate costs and occurrence of potential resource misplacement., Material and Methods: Observational Retrospective study conducted at the Santo Spirito Hospital in Rome, Italy. Observation period ranged from 1/09/2022, when the local database was instituted, to 1/03/2023 (6 months). Data from admissions records was anonymously collected. Data linkage with administrative local hospital database was performed in order to identify the date a discharge request was fired for each admission. Surgical discharges and Intensive Care Unit (ICU) discharges were excluded from this study. A Poisson hierarchical regression model was employed to investigate for the role of ward, Severity of Disease (SoD) and Risk of Mortality (RoM) on elongation of discharge time., Results: 1222 medical ward admissions were recorded in the timeframe. 16% of them were considered as subject to potentially elongated stay, and a mean Delay in discharge of 6.3 days (SD 7.9) was observed., Discussion and Conclusions: Delayed discharge may cause a "bottleneck" in admissions and result in overcrowded Emergency Department, overall poor performance, and increase in overall costs. A consisted proportion of available beds can get inappropriately occupied, and this inflates both direct and indirect costs. Clinical conditions on admission are not a good predictor of delay in discharge, and the root causes of this phenomenon likely lie in organizational issues (on structure\system level) and social issues (on patient's level)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Vinci et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Trees structure the Earth's most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations 1-6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth's 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories 7 , we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world's most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees., (© 2024. The Author(s).)

Marine sediments are regarded as sinks for several classes of contaminants. Characterization and effects of sediments on marine biota now require a multidisciplinary approach, which includes chemical and ecotoxicological analyses and molecular biomarkers. Here, a gene expression study was performed to measure the response of adult females of the Mediterranean copepod Acartia clausi to elutriates of polluted sediments (containing high concentrations of polycyclic aromatic hydrocarbons, PAHs, and heavy metals) from an industrial area in the Southern Tyrrhenian Sea (Bagnoli-Coroglio). Functional annotation of the A. clausi transcriptome generated as reference here, showed a good quality of the assembly and great homology with other copepod and crustacean sequences in public databases. This is one of the few available transcriptomic resources for this widespread copepod species of great ecological relevance in temperate coastal areas. Differential expression analysis between females exposed to the elutriate and those in control seawater identified 1000 differentially expressed genes, of which 743 up- and 257 down-regulated. Within the up-regulated genes, the most represented functions were related to proteolysis (lysosomal protease, peptidase, cathepsin), response to stress and detoxification (heat-shock protein, superoxide dismutase, glutathione-S-transferase, cytochrome P450), and cytoskeleton structure (α- and β-tubulin). Down-regulated genes were mostly involved with ribosome structure (ribosomal proteins) and DNA binding (histone proteins, transcription factors). Overall, these results suggest that processes such as transcription, translation, protein degradation, metabolism of biomolecules, reproduction, and xenobiotic detoxification were altered in the copepod in response to polluted elutriates. In conclusion, our results contribute to gaining information on the transcriptomic responses of copepods to polluted sediments. They will also prompt the selection of genes of interest to be used as biomarkers of exposure to PAHs and heavy metals in molecular toxicology studies on copepods, and in general, in comparative functional genomic studies on marine zooplankton., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Non-alcoholic Fatty Liver Disease (NAFLD), now better known as Metabolic (Dysfunction)-Associated Fatty Liver Disease (MAFLD) and its progression to Nonalcoholic Steatohepatitis (NASH), more recently referred to as Metabolic (Dysfunction)-Associated Steatohepatitis (MASH) are the most common causes of liver failure and chronic liver damage. The new names emphasize the metabolic involvement both in relation to liver function and pathological features with extrahepatic manifestations. This study aims to explore the role of the immunometabolic enzyme ATP citrate lyase (ACLY), with a critical function in lipogenesis, carbohydrate metabolism, gene expression and inflammation., Methods: ACLY function was investigated in TNFα-triggered human hepatocytes and in PBMC-derived macrophages from MASH patients. Evaluation of expression levels was carried out by western blotting and/or RT-qPCR. In the presence or absence of ACLY inhibitors, ROS, lipid peroxidation and GSSG oxidative stress biomarkers were quantified. Chromatin immunoprecipitation (ChIP), transient transfections, immunocytochemistry, histone acetylation quantitation were used to investigate ACLY function in gene expression reprogramming. IL-6 and IL-1β were quantified by Lumit immunoassays., Results: Mechanistically, ACLY inhibition reverted lipid accumulation and oxidative damage while reduced secretion of inflammatory cytokines in TNFα-triggered human hepatocytes. These effects impacted not only on lipid metabolism but also on other crucial features of liver function such as redox status and production of inflammatory mediators. Moreover, ACLY mRNA levels together with those of malic enzyme 1 (ME1) increased in human PBMC-derived macrophages from MASH patients when compared to age-matched healthy controls. Remarkably, a combination of hydroxycitrate (HCA), the natural ACLY inhibitor, with red wine powder (RWP) significantly lowered ACLY and ME1 mRNA amount as well as IL-6 and IL-1β production in macrophages from subjects with MASH., Conclusion: Collectively, our findings for the first time highlight a broad spectrum of ACLY functions in liver as well as in the pathogenesis of MASH and its diagnostic and therapeutic potential value., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: To propose a novel framework for COVID-19 vaccine allocation based on three components of Vulnerability, Vaccination, and Values (3Vs)., Methods: A combination of geospatial data analysis and artificial intelligence methods for evaluating vulnerability factors at the local level and allocate vaccines according to a dynamic mechanism for updating vulnerability and vaccine uptake., Results: A novel approach is introduced including (I) Vulnerability data collection (including country-specific data on demographic, socioeconomic, epidemiological, healthcare, and environmental factors), (II) Vaccination prioritization through estimation of a unique Vulnerability Index composed of a range of factors selected and weighed through an Artificial Intelligence (AI-enabled) expert elicitation survey and scientific literature screening, and (III) Values consideration by identification of the most effective GIS-assisted allocation of vaccines at the local level, considering context-specific constraints and objectives., Conclusions: We showcase the performance of the 3Vs strategy by comparing it to the actual vaccination rollout in Kenya. We show that under the current strategy, socially vulnerable individuals comprise only 45% of all vaccinated people in Kenya while if the 3Vs strategy was implemented, this group would be the first to receive vaccines., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Shayegh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Strobilurins represent the most widely used class of fungicides nowadays andare considered relatively non-toxic to mammals and birds but highly toxic to aquatic biota. Dimoxystrobin is one of the novel strobilurins, recently included in the 3rd Watch List of the European Commission as available data indicate that it could pose a significant risk to aquatic species. As yet, the number of studies explicitly assessing the impact of this fungicide on terrestrial and aquatic species is extremely low, and the toxic effects of dimoxystrobin on fish have not been reported. Here we investigate for the first time the alterations induced by two environmentally relevant and very low concentrations of dimoxystrobin (6.56 and 13.13 μg/L) in the fish gills. morphological, morphometric, ultrastructural, and functional alterations have been evaluated using zebrafish as a model species. We demonstrated that even short-term exposure (96 h) to dimoxystrobin alters fish gills reducing the surface available for gas exchange and inducing severe alterations encompassing three reaction patterns: circulatory disturbance and both regressive and progressive changes. Furthermore, we revealed that this fungicide impairs the expression of key enzymes involved in osmotic and acid-base regulation (Na + /K + -ATPase and AQP3) and the defensive response against oxidative stress (SOD and CAT). The information presented here highlights the importance of combining data from different analytical methods for evaluating the toxic potential of currently used and new agrochemical compounds. Our results will also contribute to the discussion on the suitability of mandatory ecotoxicological tests on vertebrates before the introduction on the market of new compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Sustainability issues such as food insecurity, climate change, land degradation, economic development and food waste are the actual most important challenges at the global level. Among them, the food waste (FW) challenge has a great magnitude, emphasizing the importance of examining this issue. Specifically, there is a need to focus on the household level. Thus, this study aims to investigate and identify the main factors influencing FW household behaviors on which policymakers and stakeholders could outline specific and sustainable strategies. Starting from a large number of published studies on this subject with a similar aim but focusing on specific Countries or contexts, the goal of our study is achieved through the implementation of a systematic literature review followed by a bibliometric review using the VOSviewer software. The selected query generated a total of 235 matching papers from which only 111 papers were collected for the bibliometric review because of the inclusion criteria. The analysis showed the existence of four major research strands: the largest one analyses the antecedents of behavior during food management, including the implementation of the Theory of Planned Behavior (TPB). Other detected topics are the economic impact of FW, the effects generated by the Covid-19 pandemic on consumer behaviors, and finally, the environmental and social effects of FW. The objective of this study is to investigate and identify the main factors influencing FW household behaviors. The obtained output represents useful information for policymakers and stakeholders to outline specific and sustainable strategies to reduce FW., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Pilone et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Young children are at increased risk of severe illness from influenza and pneumococcal infections. The World Health Organization (WHO) recommends vaccination with influenza and pneumococcal conjugate vaccine (PCV). However, in Singapore, vaccine uptake remains suboptimal relative to other routine childhood immunisations. Limited information exists regarding determinants of influenza and pneumococcal vaccine uptake in children. We estimated vaccine uptake and investigated factors associated with influenza and pneumococcal vaccination status by age group using data from a cohort study on acute respiratory infections in children attending preschools in Singapore. We recruited children aged two to six years at 24 participating preschools from June 2017 to July 2018. We determined the proportion of children immunised with influenza vaccine and PCV, and investigated socio-demographic factors associated with vaccine uptake using logistic regression models. Among 505 children, 77.5% were of Chinese ethnicity, and 53.1% were male. History of influenza vaccination was 27.5% of which 11.7% had been vaccinated within the past 12 months. In multivariable analyses, factors associated with influenza vaccine uptake were 'children living in landed property' (aOR = 2.25, 95% CI [1.07-4.67]) and 'history of hospitalisation due to cough' (aOR = 1.85, 95% CI [1.00-3.36]). Nearly three-quarters of participants (70.7% 95%CI: [66.6-74.5]) reported prior PCV vaccination. PCV uptake was higher for younger children. 'Higher parental education' (OR = 2.83, 95% CI [1.51,5.32]), 'household income' (OR = 1.26, 95% CI [1.08,1.48]) and 'smokers in household' (OR = 0.48, 95% CI [0.31,0.74]) were significantly associated with PCV uptake in univariable analyses. Only 'smokers in household' remained significantly associated with PCV uptake (aOR = 0.55, 95% CI [0.33,0.91]) in the adjusted model. Our results indicate that episodes of severe respiratory illness are a cue to influenza vaccination suggesting that doctors are more likely to recommend influenza vaccines to high-risk children. For PCV, our findings suggest overall greater awareness and education on the benefit of PCV vaccination is required., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zahari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Even though numerous Histone deacetylase inhibitors (HDACi) have been approved for the treatment of different types of cancer, and others are in clinical trials for the treatment of neurodegenerative diseases, the main problem related to the clinical use of available HDACi is their low isoform selectivity which causes undesirable effects and inevitably limits their therapeutic application. Previously, we demonstrated that a standardized Zingiber officinalis Roscoe rhizome extract (ZOE) reduced neuroinflammation through HDAC1 inhibition in a mice model of neuropathy, and this activity was related to terpenes fraction., Hypothesis/purpose: The aim of this work was to identify the ZOE constituent responsible for the activity on HDAC1 and to study its possible application in trauma-induced neuropathic pain., Methods: The ability of ZOE and its terpenes fraction (ZTE) to inhibit HDAC and SIRT isoforms activity and protein expression was assessed in vitro. Then, a structure-based virtual screening approach was applied to predict which constituent could be responsible for the activity. In the next step, the activity of selected compound was tested in an in vitro model of neuroinflammation and in an in vivo model of peripheral neuropathy (SNI)., Results: ZTE resulted to be more potent than ZOE on HDAC1, 2, and 6 isoforms, while ZOE was more active on HDAC8. Zingiberene (ZNG) was found to be the most promising HDAC1 inhibitor, with an IC 50 of 2.3 ± 0.1 µM. A non-zinc-binding mechanism of inhibition was proposed based on molecular docking. Moreover, the oral administration of ZNG reduced thermal hyperalgesia and mechanical allodynia in animals with neuropathy after 60 min from administration, and decreased HDAC-1 levels in the spinal cord microglia., Conclusion: We found a new non-zinc-dependent inhibitor of HDAC class I, with a therapeutic application in trauma-related neuropathic pain forms in which microglia-spinal overexpression of HDAC1 occurs. The non-zinc-binding mechanism has the potential to reduce off target effects, leading to a higher selectivity and better safety profile, compared to other HDAC inhibitors., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Introduction: Cenobamate is a new antiseizure medication (ASM) recently introduced in the USA for the treatment of adults with focal-onset seizures. In March 2021, the European Commission authorized its use for the adjunctive treatment of focal-onset seizures with or without secondary generalization (focal seizures with or without progression to bilateral tonic-clonic seizures, according to current ILAE terminology) in adults with epilepsy not adequately controlled despite the treatment with at least two ASMs., Areas Covered: This review summarizes the mechanism of action, efficacy, and safety of Cenobamate. The authors provide their expert opinions on the use of this drug., Expert Opinion: The aim of this paper is to report on the Italian preliminary experience with the use of cenobamate, focusing on treatment goals, optimal dosing and titration schedules, strategies to minimize adverse effects, and identification of suitable candidates for treatment. There was agreement that slow titration may improve tolerability, and that clinically significant benefit can be achieved in many patients at relatively low doses. A favorable response to relatively low doses of cenobamate could be an early predictor of ultimate responsiveness. Overall, cenobamate is a welcome new treatment for adults with focal seizures resistant to conventional ASMs.

Heavy metal contamination is recognized worldwide as a serious threat to human health and wildlife, and reducing their emissions is a priority of international and EU actions. Due to its persistence, high bioaccumulation tendency, and toxicity properties, lead (Pb) is one of the heavy metals of greatest concern. Even at low concentrations, lead induces various clinical and subclinical conditions in both humans and animals, and it has been included in the priority list of hazardous substances. In the present study, we used zebrafish's early stages as a model, given their well-acknowledged predictive value in the risk assessment of chemicals. This study was designed to investigate the morphological and morphometric alterations induced by Pb during zebrafish's early development and disclose the putative effects stage- and/or dose-dependent. We examined injuries induced by two environmentally relevant and extremely low concentrations of Pb (2.5 μg/L and 5 μg/L) during two exposure windows: early (between 1 and 7 dpf) and late (between 2 and 8 dpf). We clearly demonstrated that the incidence and severity of morphological abnormalities increased with increasing Pb dose and exposure time in both early and late-exposed groups. Furthermore, we revealed that malformation severity was significantly higher in the early exposed group than in the late exposure group at all exposure times and for both tested doses, thus highlighting the high sensitivity of zebrafish during the initial stages of development. The information presented in this paper emphasizes the effectiveness of morphological biomarkers in unveiling threatening situations and supports the role of zebrafish embryos and larvae in risk assessment and environmental monitoring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Coronary artery disease (CAD) is the single most common cause of death worldwide. Recent technological developments with coronary cardiovascular magnetic resonance angiography (CCMRA) allow high-resolution free-breathing imaging of the coronary arteries at submillimeter resolution without contrast in a predictable scan time of ~ 10 min. The objective of this study was to determine the diagnostic accuracy of high-resolution CCMRA for CAD detection against the gold standard of invasive coronary angiography (ICA)., Methods: Forty-five patients (15 female, 62 ± 10 years) with suspected CAD underwent sub-millimeter-resolution (0.6 mm 3 ) non-contrast CCMRA at 1.5T in this prospective clinical study from 2019-2020. Prior to CCMR, patients were given an intravenous beta blockers to optimize heart rate control and sublingual glyceryl trinitrate to promote coronary vasodilation. Obstructive CAD was defined by lesions with ≥ 50% stenosis by quantitative coronary angiography on ICA., Results: The mean duration of image acquisition was 10.4 ± 2.1 min. On a per patient analysis, the sensitivity, specificity, positive predictive value and negative predictive value (95% confidence intervals) were 95% (75-100), 54% (36-71), 60% (42-75) and 93% (70-100), respectively. On a per vessel analysis the sensitivity, specificity, positive predictive value and negative predictive value (95% confidence intervals) were 80% (63-91), 83% (77-88), 49% (36-63) and 95% (90-98), respectively., Conclusion: As an important step towards clinical translation, we demonstrated a good diagnostic accuracy for CAD detection using high-resolution CCMRA, with high sensitivity and negative predictive value. The positive predictive value is moderate, and combination with CMR stress perfusion may improve the diagnostic accuracy. Future multicenter evaluation is now required., (© 2022. The Author(s).)

Introduction: Status epilepticus (SE) in pregnancy represents a life-threatening medical emergency for both mother and fetus. Pregnancy-related pharmacokinetic modifications and the risks for fetus associated with the use of antiseizure medications (ASMs) and anesthetic drugs complicate SE management. No standardized treatment protocol for SE in pregnancy is available to date., Areas Covered: In this review, we provide an overview of the current literature on the management of SE in pregnancy and we propose a multidisciplinary-based protocol approach., Expert Opinion: Literature data are scarce (mainly anecdotal case reports or small case series). Prompt treatment of SE during pregnancy is paramount and a multidisciplinary team is needed. Benzodiazepines are the drugs of choice for SE in pregnancy. Levetiracetam and phenytoin represent the most suitable second-line agents. Valproic acid should be administered only if other ASMs failed and preferably avoided in the first trimester of pregnancy. For refractory SE, anesthetic drugs are needed, with propofol and midazolam as preferred drugs. Magnesium sulfate is the first-line treatment for SE in eclampsia. Termination of pregnancy, via delivery or abortion, is recommended in case of failure of general anesthetics. Further studies are needed to identify the safest and most effective treatment protocol.

Background: Vaccination is expected to change the epidemiology and management of SARS-CoV-2 epidemics., Methods: We used an age-stratified compartmental model calibrated to French data to anticipate these changes and determine implications for the control of an autumn epidemic. We assumed vaccines reduce the risk of hospitalization, infection, and transmission if infected by 95%, 60%, and 50%, respectively., Results: In our baseline scenario characterized by basic reproduction number R 0 =5 and a vaccine coverage of 70-80-90% among 12-17, 18-59, and ≥ 60 years old, important stress on healthcare is expected in the absence of measures. Unvaccinated adults ≥60 years old represent 3% of the population but 43% of hospitalizations. Given limited vaccine coverage, children aged 0-17 years old represent a third of infections and are responsible for almost half of transmissions. Unvaccinated individuals have a disproportionate contribution to transmission so that measures targeting them may help maximize epidemic control while minimizing costs for society compared to non-targeted approaches. Of all the interventions considered including repeated testing and non-pharmaceutical measures, vaccination of the unvaccinated is the most effective., Conclusions: With the Delta variant, vaccinated individuals are well protected against hospitalization but remain at risk of infection and should therefore apply protective behaviors (e.g., mask-wearing). Targeting non-vaccinated individuals may maximize epidemic control while minimizing costs for society. Vaccinating children protects them from the deleterious effects of non-pharmaceutical measures. Control strategies should account for the changing SARS-CoV-2 epidemiology., (© 2022. The Author(s).)

There are a few reported cases of isolated localized metastasis to bone arising from cancer of uterine cervix in the literature. This is a case of uterine cervix cancer with isolated metastasis to the humerus. A 57-year-old female with a diagnosis of FIGO Stage IIB invasive squamous cell carcinoma of uterine cervix underwent neoadjuvant chemoradiation therapy (CRT) and radical surgery with complete pathological response. Nine months after the surgery, a total body positron emission tomography/computed tomography (PET/CT) scan documented a lesion localized in the proximal part of the right humerus, whereas no evidence of skeletal metastasis found elsewhere. The biopsy from the bone lesion showed a metastatic squamous cell carcinoma of the uterine cervix. A surgical excision of the humeral lesion plus chemotherapy and zoledronic acid was performed. After 9 months, the patient experienced liver metastases and died 2 months later. Bone metastasis is not so infrequent in patients with locally advanced cervical cancer. Total body PET/CT scan should be included in staging work up, and an appropriate treatment should have the primary objective of quality of life preservation., Competing Interests: None