In vitro and in vivo biocompatibility of boron/nitrogen co-doped carbon nano-onions

Boron/nitrogen, co-doped, carbon nano-onions (BN-CNOs) have recently shown great promise as catalysts for the oxygen reduction reaction, due to the improved electronic properties imparted by the dopant atoms; however, the interactions of BN-CNOs with biological systems have not yet been explored. In this study, we examined the toxicological profiles of BN-CNOs and oxidized BN-CNOs (oxi-BN-CNOs) in vitro in both healthy and cancer cell lines, as well as on the embryonic stages of zebrafish (Danio rerio) in vivo. The cell viabilities of both cell lines cells were not affected after treatment with different concentrations of both doped CNO derivatives. On the other hand, the analysis of BN-CNOs and oxidized BN-CNO interactions with zebrafish embryos did not report any kind of perturbations, in agreement with the in vitro results. Our results show that both doped CNO derivatives possess a high biocompatibility and biosafety in cells and more complex systems. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Optimising the observation of optical kilonovae with medium size telescopes

We consider the optimisation of the observing strategy (cadence, exposure time and filter choice) using medium size (2-m class) optical telescopes in the follow-up of kilonovae localised with arcminute accuracy to be able to distinguish among various kilonova models and viewing angles. To develop an efficient observation plan, we made use of the synthetic light curves obtained with the Monte Carlo radiative transfer code POSSIS for different kilonova models and as a function of different viewing angles and distances. By adding the appropriate photon counting noise to the synthetic light curves, we analysed four alternative sequences having the same total time exposure of 8 hours, with different time windows (0.5, 1, 2, 4 h), each with $i$, $r$, and $u$ filters, to determine the observing sequence that maximises the chance of a correct identification of the model parameters. We suggest to avoid $u$ filter and to avoid the use of colour curves. We also found that, if the error on distance is $\le$ 2%, 0.5, 1, 2-hour time window sequences are equivalent, so we suggest to use 2-hour one, because it has 1 day cadence, so it can be easily realised. When the distance of the source is unknown, 0.5 h time window sequence is preferable.Comment: 9 pages, 8 figures, published in MNRA

Structure and dynamics of nanoconfined water and aqueous solutions

This review is devoted to discussing recent progress on the structure, thermodynamic, reactivity, and dynamics of water and aqueous systems confined within different types of nanopores, synthetic and biological. Currently, this is a branch of water science that has attracted enormous attention of researchers from different fields interested to extend the understanding of the anomalous properties of bulk water to the nanoscopic domain. From a fundamental perspective, the interactions of water and solutes with a confining surface dramatically modify the liquid's structure and, consequently, both its thermodynamical and dynamical behaviors, breaking the validity of the classical thermodynamic and phenomenological description of the transport properties of aqueous systems. Additionally, man-made nanopores and porous materials have emerged as promising solutions to challenging problems such as water purification, biosensing, nanofluidic logic and gating, and energy storage and conversion, while aquaporin, ion channels, and nuclear pore complex nanopores regulate many biological functions such as the conduction of water, the generation of action potentials, and the storage of genetic material. In this work, the more recent experimental and molecular simulations advances in this exciting and rapidly evolving field will be reported and critically discussed

GRB minimum variability timescale with Insight-HXMT and Swift: implications for progenitor models, dissipation physics and GRB classifications

The dissipation process of GRB prompt emission is still unknown. Study of temporal variability may provide a unique way to discriminate the imprint of the inner engine activity from geometry and propagation related effects. We define the minimum variability timescale (MVT) as the shortest duration of individual pulses that shape a light curve for a sample of GRBs and test correlations with peak luminosity, Lorentz factor, and jet opening angle. We compare these correlations with predictions from recent numerical simulations for a relativistic structured -- possibly wobbling -- jet and assess the value of MTV as probe of prompt-emission physics. We used the peak detection algorithm mepsa to identify the shortest pulse within a GRB time history and estimate its full width half maximum (FWHM). We applied this framework to two sets of GRBs: Swift (from 2005 to July 2022) and Insight-HXMT (from June 2017 to July 2021, including 221009A). We then selected 401 GRBs with measured z to test for correlations. On average short GRBs have significantly shorter MVT than long GRBs. The MVT distribution of short GRBs with extended emission such as 060614 and 211211A is compatible only with that of short GRBs. This provides a new clue on the progenitor's nature. The MVT for long GRBs anticorrelates with peak luminosity. We confirm the anticorrelation with the Lorentz factor and find a correlation with the jet opening angle as estimated from the afterglow, along with an inverse correlation with the number of pulses. The MVT can identify the emerging putative new class of long GRBs that are suggested to be produced by compact binary mergers. For otherwise typical long GRBs, the different correlations between MVT and peak luminosity, Lorentz factor, jet opening angle, and number of pulses can be explained within the context of structured, possibly wobbling, weakly magnetised relativistic jets. (summarised)Comment: 18 pages, 15 figures, accepted by A&

Identification of thyroid tumor cell vulnerabilities through a siRNA-based functional screening

The incidence of thyroid carcinoma is rapidly increasing. Although generally associated with good prognosis, a fraction of thyroid tumors are not cured by standard therapy and progress to aggressive forms for which no effective treatments are currently available. In order to identify novel therapeutic targets for thyroid carcinoma, we focused on the discovery of genes essential for sustaining the oncogenic phenotype of thyroid tumor cells, but not required to the same degree for the viability of normal cells (non-oncogene addiction paradigm). We screened a siRNA oligonucleotide library targeting the human druggable genome in thyroid cancer BCPAP cell line in comparison with immortalized normal human thyrocytes (Nthy-ori 3-1). We identified a panel of hit genes whose silencing interferes with the growth of tumor cells, while sparing that of normal ones. Further analysis of three selected hit genes, namely Cyclin D1, MASTL and COPZ1, showed that they represent common vulnerabilities for thyroid tumor cells, as their inhibition reduced the viability of several thyroid tumor cell lines, regardless the histotype or oncogenic lesion. This work identified non-oncogenes essential for sustaining the phenotype of thyroid tumor cells, but not of normal cells, thus suggesting that they might represent promising targets for new therapeutic strategies

Primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease. PBC primarily affects women (female preponderance 9–10:1) with a prevalence of up to 1 in 1,000 women over 40 years of age. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The diagnosis is based on sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase and gamma-glutamyl transferase, and the presence of serum antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex. Histologically, PBC is characterized by florid bile duct lesions with damage to biliary epithelial cells, an often dense portal inflammatory infiltrate and progressive loss of small intrahepatic bile ducts. Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at adequate doses of 13–15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. The mode of action of UDCA is still under discussion, but stimulation of impaired hepatocellular and cholangiocellular secretion, detoxification of bile, and antiapoptotic effects may represent key mechanisms. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarizes current knowledge on the clinical, diagnostic, pathogenetic, and therapeutic aspects of PBC

A case of isoniazid-induced delirium

This is the first report of a case of isoniazide-induced pure delirium, with all clinical features according to DSM -IV criteria. We also confirmed successful resolutions of symptoms only by discontinuation of isoniazid therapy

Effect of trehalose on protein cryoprotection: Insights into the mechanism of slowing down of hydration water

We study, with molecular dynamics simulations, a lysozyme protein immersed in a water-trehalose solution upon cooling. The aim is to understand the cryoprotectant role played by this disaccharide through the modifications that it induces on the slow dynamics of protein hydration water with its presence. The alpha -relaxation shows a fragile to strong crossover about 20 degrees higher than that in the bulk water phase and 15 degrees higher than that in lysozyme hydration water without trehalose. The protein hydration water without trehalose was found to show a second slower relaxation exhibiting a strong to strong crossover coupled with the protein dynamical transition. This slower relaxation time importantly appears enormously slowed down in our cryoprotectant solution. On the other hand, this long-relaxation in the presence of trehalose is also connected with a stronger damping of the protein structural fluctuations than that found when the protein is in contact with the pure hydration water. Therefore, this appears to be the mechanism through which trehalose manifests its cryoprotecting function