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Annarita Falanga,1 Antonietta Siciliano,2 Mariateresa Vitiello,3 Gianluigi Franci,4 Valentina Del Genio,5 Stefania Galdiero,5 Marco Guida,2 Federica Carraturo,2 Amir Fahmi,6,* Emilia Galdiero2,* 1Department of Agricultural Science, University of Naples Federico II, Portici 80055, Italy; 2Department of Biology, University of Naples Federico II, Naples 80100, Italy; 3Department of Clinical Pathology, Virology Unit, “San Giovanni di Dio e Ruggi d’Aragona Hospital”, Salerno, Italy; 4Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana,” University of Salerno, Baronissi, Italy; 5Department of Pharmacy, School of Medicine, University of Naples Federico II, Naples 80134, Italy; 6Rhein-Waal University of Applied Sciences, Kleve D-47533, Germany*These authors contributed equally to this workCorrespondence: Emilia Galdiero; Amir Fahmi Tel +39081679182Email egaldier@unina.it; Amir.fahmi@hochschule-Rhein-Waal.deBackground: Metallic nanoparticles (NPs) are highly exploited in manufacturing and medical processes in a broad spectrum of industrial applications and in the academic sectors. Several studies have suggested that many metallic nanomaterials including those derived by silver (Ag) are entering the ecosystem to cause significant toxic consequences in cell culture and animal models. However, ecotoxicity studies are still receiving limited attention when designing functionalized and non.-functionalized AgNPs.Objective: This study aimed to investigate different ecotoxicological profiles of AgNPs, which were analyzed in two different states: in pristine form uncoated AgNPs and coated AgNPs with the antimicrobial peptide indolicidin. These two types of AgNPs are exploited for a set of different tests using Daphnia magna and Raphidocelis subcapitata, which are representatives of two different levels of the aquatic trophic chain, and seeds of Lepidium sativum, Cucumis sativus and Lactuca sativa.Results: Ecotoxicological studies showed that the most sensitive organism to AgNPs was crustacean D. magna, followed by R. subcapitata and plant seeds, while AgNPs coated with indolicidin (IndAgNPs) showed a dose-dependent decreased toxicity for all three.Conclusion: The obtained results demonstrate that high ecotoxicity induced by AgNPs is strongly dependent on the surface chemistry, thus the presence of the antimicrobial peptide. This finding opens new avenues to design and fabricate the next generation of metallic nanoparticles to ensure the biosafety and risk of using engineered nanoparticles in consumer products.Keywords: silver nanoparticles, antimicrobial peptide indolicidin, in vivo toxicity, phytotoxicity, nanotoxicology

Study Region: Cerkniško Polje, (SW Slovenia) - regularly flooded polje with a complex recharge and partly disturbed due to human interventions. Study Focus: We focus on the long-term flooding dynamics on the polje, including analyses of trends over time, seasonal changes and identification of the impact of climate change and human construction activities on the flooding dynamics. For this purpose, we used a 70 years long dataset of continuous hydrological and meteorological measurements, and analysed documents about past human activities on the polje. New Hydrological Insights for the Region: Comprehensive analyses have revealed notable changes in the flood dynamics over past decades which mostly reflect a general drop of the water level. This is linked to both changes in the climate (lower effective precipitation) and human construction activities (regulation of the river beds, construction of dams, widening or reclogging of swallow holes). In the 1970s floods were longer and more extensive due to experimental permanent lake formation but since the partial removal of constructions, floods have become shorter and less extensive, although extreme events are more frequent than in the past. These changing patterns further impact on biodiversity, which is one of the most remarkable elements of the polje.

Study Question: Is the microRNA (miRNA) expression pattern of cumulus oophorus cells (COCs) in women undergoing medically assisted reproduction (MAR) procedures differentially modulated according to patient age and gonadotropin treatment strategy?Summary Answer: Maternal age is an independent factor impacting miRNA expression in COCs while gonadotropin treatment may affect follicular miRNA expression and IVF efficacy.What Is Known Already: Epigenetic mechanisms in female infertility are complex and poorly studied. DNA methylation, histone modifications, miRNAs and nucleosome positioning influence cellular machinery through positive and negative feedback mechanisms either alone or interactively. miRNAs are important regulators during oogenesis, spermatogenesis and early embryogenesis, and are reported to play a role in regulating crosstalk between the oocyte and COCs. Although miRNome analysis has been performed in female human reproductive tissues (endometrium, myometrium, cervix and ovaries), epigenetic modifications in women with infertility have not been explored in detail. In addition, the impact of gonadotropin treatments during MAR on miRNA expression in COCs has not been fully investigated.Study Design, Size, Duration: This study was carried out in 53 COC samples obtained from mature metaphase II (MII) oocytes in 53 women undergoing MAR treatment. A total of 38 samples for assay development were pooled by maternal age and gonadotropin treatment into four predetermined subgroups: ≥36 years and recombinant human FSH (r-hFSH), n = 10; ≥36 years and r-hFSH+ recombinant human-luteinizing hormone (r-hLH), n = 10; ≤35 years and r-hFSH, n = 9; ≤35 years and r-hFSH+r-hLH, n = 9. miRNome profiles were determined and compared between subgroups. Expression of defined miRNAs was validated in the remaining fifteen samples, representative of each subgroup, by quantitative polymerase chain reaction (PCR).Participants/materials, Setting, Methods: COCs were processed for miRNA-enriched total RNA extraction and pooled in homogeneous subgroups to obtain a sufficient amount and quality of starting material to perform the analysis. Each pooled sample underwent miRNA profiling using PCR assay system to examine expression of 752 human miRNAs without pre-amplification. Data were analyzed using the delta-delta Ct method for relative quantitation and prediction of target genes (with at least four algorithms predicting the same miRNA-gene interaction pair (HIT)>4). The miRSystem database provided functional annotation enrichment (raw P-value <0.05) of co-expressed miRNAs.Main Results and the Role Of Chance: We found distinctive miRNA expression profiles in each subgroup correlating with age and MAR stimulation. In addition, a number of selective and co-expressed miRNAs were revealed by comparative analysis. A cluster of 37 miRNAs were commonly but differentially expressed in all four pools. Significant differences were observed in expression regulation of 37 miRNAs between age groups (≤35 or ≥36) in women receiving r-hFSH+r-hLH compared to those receiving r-hFSH alone. Higher concentrations and increased numbers of miRNAs were recorded in younger than in older patients, regardless of treatment. Functional and expression studies performed to retrieve common miRNome profiles revealed an enrichment of biological functions in oocyte growth and maturation, embryo development, steroidogenesis, ovarian hyperstimulation, apoptosis and cell survival, glucagon and lipid metabolism, and cell trafficking. The highest scored pathways of target genes of the 37 common miRNAs were associated with mitogen-activated protein kinase (MAPK) signaling pathways, G alpha signaling, transcription regulation, tight junctions, RNA polymerase I and III, and mitochondrial transcription. We identified a potential age- and MAR stimulation-dependent signature in the miRNA landscape of COCs.Limitations, Reasons For Caution: We cannot rule out the possibility that other unknown individual genetic or clinical factors may have interfered with the reported results. Since miRNA profiling was conducted with a predefined array of target probes, other miRNA molecules, potentially modulated by age and hormonal stimulation, may have been missed in this study.Wider Implications Of the Findings: miRNA expression in COCs is modulated by gonadotropin treatment and correlates strongly with age. A better understanding of the expression patterns and functions of miRNAs may lead to the development of novel therapeutics to treat ovarian dysfunction and improve fertility in older women.Study Funding/competing Interest: This study was funded by Merck KGaA, Darmstadt, Germany. All authors declared no competing interest, except SL and TD who are fully employed by Merck KGaA.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has proved to be one of the most challenging infectious diseases in the modern era, and despite several countermeasures to lessen its impact, the spread of the virus is still affecting most countries. This renders the goal of active immunization of the population through vaccination a worldwide public health priority. In fact, only when efficient vaccination programs will be successfully implemented, a return to pre-pandemic normality can be considered. The scientific community has made a tremendous effort to blow the lid off the pathogenesis of the disease, and unprecedented efforts are ongoing with governments, private organizations, and academics working together to expeditiously develop safe and efficacious vaccines. Previous research efforts in the development of vaccines for other coronaviruses (Severe Acute Respiratory Syndrome Coronavirus 1 and Middle East Respiratory Syndrome Coronavirus) as well other emerging viruses have opened the door for exploiting several strategies to design a new vaccine against the pandemic virus. Indeed, in a few months, a stunning number of vaccines have been proposed, and almost 50 putative vaccine candidates have entered clinical trials. The different vaccine candidates use different vaccine development platforms, from inactivated whole virus vaccine to subunit vaccine, nucleic acid, and vectored vaccines. In this review, we describe strengths, flaws, and potential pitfalls of each approach to understand their chances of success. [ABSTRACT FROM AUTHOR]

The aquifers of alpine karst and high karst plateaus are abundant water resources. They are difficult to characterise due to their complex, partly glaciokarstic, evolution in active tectonic environments, and an unsaturated zone up to two kilometres thick. We present and discuss the results of a tracing test in the alpine karst of the Julian Alps (Slovenia), more precisely in the Migovec System, the longest cave system in Slovenia (length = 43 km, depth = 972 m). The cave extends below a mountain ridge that separates the Soča and Sava Valleys, thus forming a topographic divide between the Adriatic and Black Sea basins, which gives the test greater regional significance. In early September 2019, three kilograms of uranine were injected into a perched lake in a remote part of the system, approximately 900 metres below the plateau and 100 metres above the low water table. All known springs in the valleys on either side of the mountain were monitored by manual or instrumental sampling and a field fluorometer. Due to the unexpectedly dry season, no tracer was detected at any site for two months until a heavy rainfall event in early November. Subsequently, about 60-65 % of the tracer mass appeared within 60 hours in the Tolminka River. No tracer was detected at other sites, either because it was not present or because it was highly diluted. The study suggests that the lake containing the tracer is bypassed by the vadose flow and that the tracer was only mobilised during large events when the lake became part of the epihreatic flow. The linear peak flow velocity from the injection site to the Tolminka Spring was only about 1.7 m/h. However, assuming that the tracer was only mobilised by the large rain event, the velocity would be 70 m/h. The study highlights the challenges and pitfalls of water tracing in alpine karst systems and suggests ways to avoid them.

Andrej Kranjc

The article focuses on the management of onset of hepatocellular carcinoma in hepatitis C virus patients who achieved the sustained virological response after treatment with direct acting antivirals. It mentions that despite the fact that the direct acting antivirals therapies are able to remove the hepatitis C virus from the patients, the epigenetic impact on cells persist also in absence of the virus itself.

Poljes are flat closed karst depressions prone to regular flooding. The floods can be several meters high, last for months and damage significantly human infrastructures. To predict the maximum level reached, the polje water balance needs to be implemented. This technique encounters the difficulty that important part of the inflow and outflow flowing through many poljes is ungauged, as it is challenging to measure accurately the numerous springs and ponors activating temporarily with the rise of water level. This work aims to see whether this problem can be handled and the polje water balance reconstituted. To do so, a typical Dinaric polje is equipped with several water level stations installed over its surface and in the nearby water active caves. Combining a 1*1m digital elevation model of the polje surface with water levels and inflow records of the main two springs allowed assessing the variation of flooded volume and reconstructing the water balance. The highest total inflow values reached during the observed period were of about 140-150 m3/s, with up to a third of it being ungauged. In addition, the effect of a large estavelles group on the polje inflow and outflow could be identified, and helped to characterize the outflow, with values comprised between 65 and 75 m3/s. Finally, intense rainfall over the polje flooded surface showed to be a temporary important source of inflow. The values found by the water balance analysis have been used as input and calibration data in a numerical model reproducing the flood dynamics in the polje and its surrounding aquifer. Results validated both polje water balance and conceptual hydrogeological model. They justify the significance of combining water level measurements with a digital elevation model to monitor the floods. The method can be applied to other poljes flooding in a complex way of superposed input and output signals. Finally, the places to be equipped in priority if the polje has no measurement network or if available funding is limited are discussed.

Caves and their surrounding fracture systems in the vadose zone of karst regions host a unique atmospheric environment. Understanding the airflow patterns in caves is critical to understanding the properties of the subsurface atmosphere and the chemical interactions between air, water, and rock. The most common driver of airflow in caves is the density difference between the subsurface and the outside air, known as the chimney effect. Observations show that seasonal airflow patterns in caves also depend on the geometry of passages. In this work, I present and use a numerical model of a passage embedded and thermally coupled to a rock mass to study the relationship between the airflow pattern and passage geometry. As the outside air enters the subsurface, it approaches thermal equilibrium with the rock mass along a characteristic relaxation length. This determines the temperature and density contrast between the inside and outside air, and the resulting pressure difference, which drives the airflow. In passages with non-uniform outlines and/or cross-sections, the relaxation length may depend on the flow direction, resulting in different airflow velocities in cold and warm periods for the same absolute temperature difference between the massif and the external temperature. In a passage with a V-shaped longitudinal profile, the airflow is triggered by instability which causes the feedback between the relaxation length and airflow velocity. The airflow pattern can also be altered by snow and ice. Heat transfer in the rock and the thermal inertia of the rock also change the relaxation lengths and cause hysteresis in the curve presenting the airflow velocity vs. temperature difference.