Anisotropic molecular packing of soluble C60 fullerenes in hexagonal nanocrystals obtained by solvent vapor annealing

We describe the self-assembly of soluble, chemically modified fullerene [6,6]-phenyl C₆₁ butyric acid methyl ester (PCBM) into a new crystalline phase where the C₆₀ moieties are arranged in parallel layers. Minimum C₆₀ center-to-center distance is 10 Å within the layers, and up to 15 Å perpendicular to the layers. Highly anisotropic, mesoscopic hexagonal crystals of this material, with a lateral size of many microns and a thickness below 1 μm, are obtained from chloroform solution by solvent vapor annealing, and characterized by optical microscopy and X-ray diffraction. The crystalline structure is deduced combining experimental data with molecular modeling and ab initio calculations. The large difference in C₆₀–C₆₀ spacing indicates a high anisotropy in electrical and charge transport properties of this new phase.     

Does carbon nanopowder threaten amphibian development?

Lethal and teratogenic potentials of carbon nanoparticles (CNPs) in their amorphous form were investigated by the standardized Frog Embryo Teratogenesis Assay-Xenopus (FETAX), a 96-h in vitro whole-embryo toxicity test based on the amphibian Xenopus laevis. Embryos were acutely exposed to 1, 10, 100 and 500 mg/L CNP suspensions and evaluated for lethality, malformations and growth inhibition. Larvae were processed for histological and ultrastructural analyses to detect the main affected organs, to look for specific lesions at the subcellular level and to image and track CNPs into tissues. Only the highest CNP suspension resulted in being embryolethal for X. laevis larvae, while malformed larva percentages significantly differed from controls starting from 100 mg/L. The stomach and gut were the preferential CNP accumulation sites, on the contrary, the digestive epithelium remained intact. The analyses showed the presence of isolated nanoparticles and/or aggregates in different secondary target organs. CNPs were found in circulating erythrocytes. The research confirms the good tolerance of X. laevis towards pure elemental carbon in its nanoparticulate amorphous form, but highlights the possibility of CNP transfer toward all body areas.     

Inherently fluorescent polyaniline nanoparticles in a dynamic landscape

In this paper we report for the first time on the emissive behavior of two polyaniline (PANI) nanoparticle systems produced via oxidative chemical polymerization in the presence of either poly(vinyl alcohol) (PVA) or chitosan as polymeric stabilizers in water. The emission from PANI nanoparticles is irreversibly quenched by an increase of pH of the suspending medium from acid to neutral (chitosan-PANI) or alkaline (PVA-PANI). Conversely, PANI nanorods synthesized in the same conditions of the above, but in presence of poly(N-vinyl pyrrolidone), is not emissive at any pH. The role of the polymeric surfactant as a soft template is key in controlling the morphology and the properties of the obtained PANI dispersions. FTIR, UV-Vis absorption and photoluminescence excitation (PLE) spectra studies suggest that the emissive properties are related to the establishment of strong, non-covalent interactions between nanoscalar PANI particles and the polymeric surfactant at the pH of synthesis. Morphology examination of the three systems, by both dynamic light scattering (DLS) and Transmission Electron Microscopy (TEM), reveal that photoluminescence is associated to the presence of a genuinely 3D nanoscalar morphology, together with an ordered disposition of PANI chains into aligned crystal planes. Concomitant to the irreversible quenching of the emission signal with increasing pH, there is an evolution of the morphology leading to particle coalescence, coarsening and ultimately phase-separation, with consequent modification of PANI-polymeric surfactant interactions, PANI chains supra-molecular organization and optical properties of the PANI nanoparticles dispersion.     

Lipid Transfer to HDL is Higher in Marathon Runners than in Sedentary Subjects,but is Acutely Inhibited During the Run

Although exercise increases HDL-cholesterol, exercise-induced changes in HDL metabolism have been little explored. Lipid transfer to HDL is essential for HDL’s role in reverse cholesterol transport. We investigated the effects of acute exhaustive exercise on lipid transfer to HDL. We compared plasma lipid, apolipoprotein and cytokine levels and in vitro transfer of four lipids from a radioactively labeled lipid donor nanoemulsion to HDL in sedentary individuals (n = 28) and in marathon runners (n = 14) at baseline, immediately after and 72 h after a marathon. While HDL-cholesterol concentrations and apo A1 levels were higher in marathon runners, LDL-cholesterol, apo B and triacylglycerol levels were similar in both groups. Transfers of non-esterified cholesterol [6.8 (5.7–7.2) vs. 5.2 (4.5–6), p = 0.001], phospholipids [21.7 (20.4–22.2) vs. 8.2 (7.7–8.9), p = 0.0001] and triacylglycerol [3.7 (3.1–4) vs. 1.3 (0.8–1.7), p = 0.0001] were higher in marathon runners, but esterified-cholesterol transfer was similar. Immediately after the marathon, LDL- and HDL-cholesterol concentrations and apo A1 levels were unchanged, but apo B and triacylglycerol levels increased. Lipid transfer of non-esterified cholesterol [6.8 (5.7–7.2) vs. 5.8 (4.9–6.6), p = 0.0001], phospholipids [21.7 (20.4–22.2) vs. 19.1 (18.6–19.3), p = 0.0001], esterified-cholesterol [3.2 (2.2–3.8) vs. 2.3 (2–2.9), p = 0.02] and triacylglycerol [3.7 (3.1–4) vs. 2.6 (2.1–2.8), p = 0.0001] to HDL were all reduced immediately after the marathon but returned to baseline 72 h later. Running a marathon increased IL-6 and TNF-α levels, but after 72 h these values returned to baseline. Lipid transfer, except esterified-cholesterol transfer, was higher in marathon runners than in sedentary individuals, but the marathon itself acutely inhibited lipid transfer. In light of these novel observations, further study is required to clarify how these metabolic changes can influence HDL composition and anti-atherogenic function.     

Statistical approaches for farm and parasitic risk profiling in geographical veterinary epidemiology

We address the problem of farm and parasitic risk profiling in the context of Veterinary Epidemiology. We take advantage of a cross-sectional study carried out in the Campania Region in order to study the spatial distribution of 16 parasites in 121 ovine farms. We propose a tri-level hierarchical Bayesian model, which account for multivariate spatially structured overdispersion, to obtain estimate of posterior classification probabilities, that is for each parasite and farm the probability to belong to the set of the null hypothesis. We explore four decision rules based on either posterior probabilities or posterior means and compare the results in terms of the number of false discoveries/non-discoveries or the rate of false discovery/non-discovery. Our approach proved useful for parasitological risk profiling and we show that decision rules can be easily handled.     

Broad-Spectrum Flavivirus Inhibitors: a Medicinal Chemistry Point of View

Infections by flaviviruses, such as Dengue, West Nile, Yellow Fever and Zika viruses, represent a growing risk for global health. There are vaccines only for few flaviviruses while no effective treatments are available. Flaviviruses share epidemiological, structural, and ecologic features and often different viruses can co-infect the same host. Therefore, the identification of broad-spectrum inhibitors is highly desirable either for known flaviviruses or for viruses that likely will emerge in the future. Strategies targeting both virus and host factors have been pursued to identify broad-spectrum antiflaviviral agents. In this review, we describe the most promising and best characterized targets and their relative broad-spectrum inhibitors, identified by drug repurposing/libraries screenings and by focused medicinal chemistry campaigns. Finally, we discuss about future strategies to identify new broad-spectrum antiflavivirus agents.     

The Anti-Inflammatory Properties of Mesenchymal Stem Cells in Epilepsy: Possible Treatments and Future Perspectives

Mesenchymal stem cells (MSCs) are multipotent adult cells with self-renewing capacities. MSCs display specific properties, such as the ability to repair damaged tissues, resulting in optimal candidates for cell therapy against degenerative diseases. In addition to the reparative functions of MSCs, growing evidence shows that these cells have potent immunomodulatory and anti-inflammatory properties. Therefore, MSCs are potential tools for treating inflammation-related neurological diseases, including epilepsy. In this regard, over the last decades, epilepsy has no longer been considered a purely neuronal pathology, since inflammatory events underlying the genesis of epilepsy have been demonstrated. This review assessed current knowledge on the use of MSCs in the treatment of epilepsy. Mostly, attention will be focused on the anti-inflammatory and immunological skills of MSCs. Understanding the mechanisms by which MSCs might modulate the severity of the disease will contribute to the development of new potential alternatives for both prophylaxis and treatment against epilepsy.     

Gangliosides in Podocyte Biology and Disease

Gangliosides constitute a subgroup of glycosphingolipids characterized by the presence of sialic acid residues in their structure. As constituents of cellular membranes, in particular of raft microdomains, they exert multiple functions, some of them capital in cell homeostasis. Their presence in cells is tightly regulated by a balanced expression and function of the enzymes responsible for their biosynthesis, ganglioside synthases, and their degradation, glycosidases. The dysregulation of their abundance results in rare and common diseases. In this review, we make a point on the relevance of gangliosides and some of their metabolic precursors, such as ceramides, in the function of podocytes, the main cellular component of the glomerular filtration barrier, as well as their implications in podocytopathies. The results presented in this review suggest the pertinence of clinical lipidomic studies targeting these metabolites.     

Dihydrotanshinone,a Natural Diterpenoid,Preserves Blood-Retinal Barrier Integrity via P2X7 Receptor

Activation of P2X7 signaling, due to high glucose levels, leads to blood retinal barrier (BRB) breakdown, which is a hallmark of diabetic retinopathy (DR). Furthermore, several studies report that high glucose (HG) conditions and the related activation of the P2X7 receptor (P2X7R) lead to the over-expression of pro-inflammatory markers. In order to identify novel P2X7R antagonists, we carried out virtual screening on a focused compound dataset, including indole derivatives and natural compounds such as caffeic acid phenethyl ester derivatives, flavonoids, and diterpenoids. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) rescoring and structural fingerprint clustering of docking poses from virtual screening highlighted that the diterpenoid dihydrotanshinone (DHTS) clustered with the well-known P2X7R antagonist JNJ47965567. A human-based in vitro BRB model made of retinal pericytes, astrocytes, and endothelial cells was used to assess the potential protective effect of DHTS against HG and 2′(3′)-O-(4-Benzoylbenzoyl)adenosine-5′-triphosphate (BzATP), a P2X7R agonist, insult. We found that HG/BzATP exposure generated BRB breakdown by enhancing barrier permeability (trans-endothelial electrical resistance (TEER)) and reducing the levels of ZO-1 and VE-cadherin junction proteins as well as of the Cx-43 mRNA expression levels. Furthermore, HG levels and P2X7R agonist treatment led to increased expression of pro-inflammatory mediators (TLR-4, IL-1β, IL-6, TNF-α, and IL-8) and other molecular markers (P2X7R, VEGF-A, and ICAM-1), along with enhanced production of reactive oxygen species. Treatment with DHTS preserved the BRB integrity from HG/BzATP damage. The protective effects of DHTS were also compared to the validated P2X7R antagonist, JNJ47965567. In conclusion, we provided new findings pointing out the therapeutic potential of DHTS, which is an inhibitor of P2X7R, in terms of preventing and/or counteracting the BRB dysfunctions elicited by HG conditions.     

Coupling hydrothermal liquefaction and aqueous phase reforming for integrated production of biocrude and renewable H2

Lignin-rich stream from lignocellulosic ethanol production was converted into biocrude by continuous hydrothermal liquefaction (HTL) while hydrogen was produced by aqueous phase reforming (APR) of the HTL aqueous by-product. The effects of Na₂CO₃ and NaOH were investigated both in terms of processability of the feedstock as well as yield and composition of the obtained products. A maximum biocrude yield of 27 wt% was reached in the NaOH-catalyzed runs. A relevant amount of dissolved phenolics were detected in the co-produced aqueous phase (AP), and removed by liquid–liquid extraction using butyl acetate or diethyl ether, preserving the APR catalyst stability and reaching an hydrogen yield up to 146 mmol H₂ L⁻¹ AP. Preliminary mass balances integrating HTL and APR showed that the hydrogen provided by APR may account for up to 46% of the hydrogen amount theoretically required for upgrading the HTL biocrude, thus significantly improving the process performance and sustainability.