Negative ozone anomalies at a high mountain site in northern Italy during 2020: a possible role of COVID-19 lockdowns?

Several studies investigated the possible impacts of the restriction measures related to the containment of the spread of the COrona VIrus Disease (COVID-19) to atmospheric ozone (O3) at global, regional, and local scales during 2020. O3 is a secondary pollutant with adverse effects on population health and ecosystems and with negative impacts on climate, acting as greenhouse gas. Most of these studies focused on spring 2020 (i.e. March–May) and on observations in the planetary boundary layer (PBL), mostly in the vicinity of urban agglomerates. Here, we analyzed the variability of O3 above the PBL of northern Italy in 2020 by using continuous observations carried out at a high mountain WMO/GAW global station in Italy (Mt. Cimone–CMN; 44°12' N, 10°42' E, 2165 m a.s.l.). Low O3 monthly anomalies were observed during spring (MAM) and summer (JJA), when periods of low O3 intertwined with periods with higher O3, within climatological ranges. A similar variability was observed for O3 precursors like NO2 and 15 anthropogenic non-methane volatile organic carbons, but the systematic O3 anomalies were not reflected in these variables. The analysis of meteorological variables and diel O3 cycles did not suggest major changes in the vertical transport related to the thermal circulation system in the mountain area. The analysis of five days back-trajectories suggested that the observed O3 anomalies cannot be explained by differences in the synoptic-scale circulation with respect to the previous years alone. On the other hand, the characterization of two transport patterns (i.e. air masses from the regional PBL or from the free troposphere) and the analysis of back-trajectories suggested an important contribution of transport from the continental PBL during the periods with the lowest O3 at CMN. When proxies of air mass transport from the regional PBL are considered, a lower NOx content was pointed out with respect to the previous years, suggesting a lower O3 production in a NOx-limited atmosphere. Our study suggested for the first time that, during MAM and JJA 2020, the reduced anthropogenic emissions related to the COVID-19 restrictions lowered the amount of this short-lived climate forcer/pollutant at remote locations above the PBL over northern Italy. This work suggests the importance of limiting anthropogenic precursor emissions for decreasing the O3 amount at remote locations and in upper atmospheric layers

Activity of Free and Liposome-Encapsulated Essential Oil from Lavandula angustifolia against Persister-Derived Biofilm of Candida auris

The high virulence of Candida auris, a pathogen fungus considered as a global threat for public health, is due to its peculiar traits such as its intrinsic resistance to conventional antifungals. Its biofilm lifestyle certainly promotes the prolonged survival of C. auris after disinfection or antifungal treatments. In this work, for the first time, we detected persister cells in a biofilm of C. auris in a microwell plate model, following caspofungin treatment. Furthermore, we showed how persisters can progressively develop a new biofilm in situ, mimicking the re-colonization of a surface which may be responsible for recalcitrant infections. Plant-derived compounds, such as essential oils, may represent a valid alternative to combat fungal infections. Here, Lavandula angustifolia essential oil, as free or encapsulated in liposomes, was used to eradicate primary and persister-derived biofilms of C. auris, confirming the great potential of alternative compounds against emergent fungal pathogens. As in other Candida species, the action of essential oils against C. auris involves ROS production and affects the expression of some biofilm-related genes

Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent.

OBJECTIVES: Drug delivery systems consisting of liposomes displaying a cell surface receptor-targeting peptide are being developed to specifically deliver chemotherapeutic drugs to tumors overexpressing a target receptor. This study addresses novel liposome composition approaches to specifically target tissues overexpressing bombesin (BN) receptors. METHODS: A new amphiphilic peptide derivative (MonY-BN) containing the BN(7-14) peptide, the DTPA (diethylenetriaminepentaacetate) chelating agent, a hydrophobic moiety with two C(18) alkyl chains, and polyethylene glycol spacers, has been synthesized by solid-phase methods. Liposomes have been generated by co-aggregation of MonY-BN with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). The structural and biological properties of these new target-selective drug-delivery systems have been characterized. RESULTS: Liposomes with a DSPC/MonY-BN (97/3 molar ratio) composition showed a diameter of 145.5 ± 31.5 nm and a polydispersity index of 0.20 ± 0.05. High doxorubicin (Dox) loading was obtained with the remote pH gradient method using citrate as the inner buffer. Specific binding to PC-3 cells of DSPC/MonY-BN liposomes was obtained (2.7% ± 0.3%, at 37°C), compared with peptide-free DSPC liposomes (1.4% ± 0.2% at 37°C). Incubation of cells with DSPC/ MonY-BN/Dox showed significantly lower cell survival compared with DSPC/Dox-treated cells, in the presence of 100 ng/mL and 300 ng/mL drug amounts, in cytotoxicity experiments. Intravenous treatment of PC-3 xenograft-bearing mice with DSPC/MonY-BN/Dox at 10 mg/kg Dox dose produced higher tumour growth inhibition (60%) compared with nonspecific DSPC/ Dox liposomes (36%) relative to control animals. CONCLUSION: The structural and loading properties of DSPC/MonY-BN liposomes along with the observed in-vitro and in-vivo activity are encouraging for further development of this approach for target-specific cancer chemotherapy

Emissions of carbon tetrachloride from Europe

Carbon tetrachloride (CCl4) is a long-lived radiatively active compound with the ability to destroy stratospheric ozone. Due to its inclusion in the Montreal Protocol on Substances that Deplete the Ozone Layer (MP), the last two decades have seen a sharp decrease in its large-scale emissive use with a consequent decline in its atmospheric mole fractions. However, the MP restrictions do not apply to the use of carbon tetrachloride as feedstock for the production of other chemicals, implying the risk of fugitive emissions from the industry sector. The occurrence of such unintended emissions is suggested by a significant discrepancy between global emissions as derived from reported production and feedstock usage (bottom-up emissions), and those based on atmospheric observations (top-down emissions). In order to better constrain the atmospheric budget of carbon tetrachloride, several studies based on a combination of atmospheric observations and inverse modelling have been conducted in recent years in various regions of the world. This study is focused on the European scale and based on long-term high-frequency observations at three European sites, combined with a Bayesian inversion methodology. We estimated that average European emissions for 2006–2014 were 2.2 (± 0.8) Gg yr−1, with an average decreasing trend of 6.9 % per year. Our analysis identified France as the main source of emissions over the whole study period, with an average contribution to total European emissions of approximately 26 %. The inversion was also able to allow the localisation of emission "hot spots" in the domain, with major source areas in southern France, central England (UK) and Benelux (Belgium, the Netherlands, Luxembourg), where most industrial-scale production of basic organic chemicals is located. According to our results, European emissions correspond, on average, to 4.0 % of global emissions for 2006–2012. Together with other regional studies, our results allow a better constraint of the global budget of carbon tetrachloride and a better quantification of the gap between top-down and bottom-up estimates

Activation of P2X7 and P2Y11 purinergic receptors inhibits migration and normalizes tumor-derived endothelial cells via cAMP signaling

Purinergic signaling is involved in inflammation and cancer. Extracellular ATP accumulates in tumor interstitium, reaching hundreds micromolar concentrations, but its functional role on tumor vasculature and endothelium is unknown. Here we show that high ATP doses (>20 μM) strongly inhibit migration of endothelial cells from human breast carcinoma (BTEC), but not of normal human microvascular EC. Lower doses (1–10 mm result ineffective. The anti-migratory activity is associated with cytoskeleton remodeling and is significantly prevented by hypoxia. Pharmacological and molecular evidences suggest a major role for P2X7R and P2Y11R in ATP-mediated inhibition of TEC migration: selective activation of these purinergic receptors by BzATP mimics the anti-migratory effect of ATP, which is in turn impaired by their pharmacological or molecular silencing. Downstream pathway includes calcium-dependent Adenilyl Cyclase 10 (AC10) recruitment, cAMP release and EPAC-1 activation. Notably, high ATP enhances TEC-mediated attraction of human pericytes, leading to a decrease of endothelial permeability, a hallmark of vessel normalization. Finally, we provide the first evidence of in vivo P2X7R expression in blood vessels of murine and human breast carcinoma. In conclusion, we have identified a purinergic pathway selectively acting as an antiangiogenic and normalizing signal for human tumor-derived vascular endothelium

Air quality and climate change: designing new win-win policies for Europe

Anthropogenic activities are responsible for the emission of gaseous and particulate pollutants that modify atmospheric composition. Such changes are, in turn, responsible for the degradation of air quality at the regional/local scale as well as for changes of climate. Air pollution and climate change are two intimately connected environmental issues. However, these two environmental challenges are still viewed as separate issues, which are dealt with by different science communities and within different policy frameworks. Indeed, many mitigation options offer the possibility to both improve air quality and mitigate climate change but, at the same time, mitigation options that may provide benefits to one aspect, are worsening the situation in the other. Therefore, coordinated actions taking into account the air quality-climate linkages are required. These actions need to be based on strong scientific grounds, as recognised by the European Commission that in the past few years has promoted consultation processes among the science community, the policy makers and the relevant stakeholders. Here, the main fields in which such coordinated actions are needed are examined from a policy perspective

Non-Methane Volatile Organic Compounds in the Background Atmospheres of a Southern European Mountain Site (Mt. Cimone, Italy): Annual and Seasonal Variability

Since January 2010 continuous high-frequency in situ measurements of a range of anthropogenic Non-Methane Volatile Organic Compounds (NMVOCs) has been carried out at the World Meteorological Organisation Global Atmospheric Watch observatory at Mt. Cimone, on the highest peak of the Italian Northern Apennines, at the border between the Po Valley and the Mediterranean Basin. Five-year (2010-2014) time series of eleven NMVOCs, including aromatic and aliphatic species, have been analysed in order to derive average mixing ratios and detect annual and seasonal variability. Recent studies conducted in Europe, mainly in urban areas, have reported a decrease in atmospheric NMVOCs. Here we investigate how the decline in emissions, due to the implementation of air pollution policies, is reflected in the annual variability of NMVOC mixing ratios measured at a regional background location. Analysis of temporal trends for wellmixed conditions showed statistically significant decreases in ethyne, n-pentane and ethyl-benzene, while no significant trends were found for propane, butanes, i-pentane, toluene and xylenes. The seasonal variability of NMVOCs has been studied showing clear seasonal cycles for longer lived compounds and cycles with smaller seasonal amplitudes for shorterlived species. We used the propane time series to describe the seasonal cycle and to verify to what extent the mixing ratios of propane have been depleted by OH oxidation. We found that, during the summer, different transport times to the receptors and different source distribution are the main responsible for the relatively low integrated OH concentrations at Mt. Cimone

Ca2+ dysregulation in cardiac stromal cells sustains fibro-adipose remodeling in Arrhythmogenic Cardiomyopathy and can be modulated by flecainide

BACKGROUND: Cardiac mesenchymal stromal cells (C-MSC) were recently shown to differentiate into adipocytes and myofibroblasts to promote the aberrant remodeling of cardiac tissue that characterizes arrhythmogenic cardiomyopathy (ACM). A calcium (Ca(2+)) signaling dysfunction, mainly demonstrated in mouse models, is recognized as a mechanism impacting arrhythmic risk in ACM cardiomyocytes. Whether similar mechanisms influence ACM C-MSC fate is still unknown. Thus, we aim to ascertain whether intracellular Ca(2+) oscillations and the Ca(2+) toolkit are altered in human C-MSC obtained from ACM patients, and to assess their link with C-MSC-specific ACM phenotypes. METHODS AND RESULTS: ACM C-MSC show enhanced spontaneous Ca(2+) oscillations and concomitant increased Ca(2+)/Calmodulin dependent kinase II (CaMKII) activation compared to control cells. This is manly linked to a constitutive activation of Store-Operated Ca(2+) Entry (SOCE), which leads to enhanced Ca(2+) release from the endoplasmic reticulum through inositol-1,4,5-trisphosphate receptors. By targeting the Ca(2+) handling machinery or CaMKII activity, we demonstrated a causative link between Ca(2+) oscillations and fibro-adipogenic differentiation of ACM C-MSC. Genetic silencing of the desmosomal gene PKP2 mimics the remodelling of the Ca(2+) signalling machinery occurring in ACM C-MSC. The anti-arrhythmic drug flecainide inhibits intracellular Ca(2+) oscillations and fibro-adipogenic differentiation by selectively targeting SOCE. CONCLUSIONS: Altogether, our results extend the knowledge of Ca(2+) dysregulation in ACM to the stromal compartment, as an etiologic mechanism of C-MSC-related ACM phenotypes. A new mode of action of flecainide on a novel mechanistic target is unveiled against the fibro-adipose accumulation in ACM. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-022-03742-8