Glycol-modified silanes: novel possibilities for the synthesis of hierarchically organized (hybrid) porous materials

The preparation of porous hierarchical architectures that have structural features spanning from the nanometer to micrometer and even larger dimensions and that exhibit certain functionalities is one of the new challenging frontiers in materials chemistry. The sol-gel process is one of the most promising synthesis routes toward such materials because it not only offers the possibility to incorporate organic functions into the porous host but also offers the possibility to deliberately tailor the pore structure. In this Account, the opportunities given by the application of novel diol-modified silanes are discussed for the synthesis of hierarchically organized inorganic and also inorganic-organic porous monoliths.     

Diatomite silica nanoparticles for drug delivery

Diatomite is a natural fossil material of sedimentary origin, constituted by fragments of diatom siliceous skeletons. In this preliminary work, the properties of diatomite nanoparticles as potential system for the delivery of drugs in cancer cells were exploited. A purification procedure, based on thermal treatments in strong acid solutions, was used to remove inorganic and organic impurities from diatomite and to make them a safe material for medical applications. The micrometric diatomite powder was reduced in nanoparticles by mechanical crushing, sonication, and filtering. Morphological analysis performed by dynamic light scattering and transmission electron microscopy reveals a particles size included between 100 and 300 nm. Diatomite nanoparticles were functionalized by 3-aminopropyltriethoxysilane and labeled by tetramethylrhodamine isothiocyanate. Different concentrations of chemically modified nanoparticles were incubated with cancer cells and confocal microscopy was performed. Imaging analysis showed an efficient cellular uptake and homogeneous distribution of nanoparticles in cytoplasm and nucleus, thus suggesting their potentiality as nanocarriers for drug delivery.

PACS

87.85.J81.05.Rm; 61.46. + w     

Soil mineral nitrogen availability predicted by herbage yield and disease resistance in red clover (<Emphasis Type="Italic">Trifolium pratense</Emphasis>) cropping

Nitrogen (N) is the most limiting nutrient in crop production. Legumes such as red clover can provide N through biofixation, but securing nitrogen in soil for subsequent crop production must also be considered. Variety selection and management in red clover cropping can influence soil mineral nitrogen (SMN) availability. A field trial to investigate this was conducted with six varieties, under one and two cut management, over 2 years. Dry matter (DM) and N yield, Sclerotinia resistance and SMN availability were assessed. Low DM and N yields (1.6–2.4 t DM ha^?1 and 54–83 kg N ha^?1) in the first year of cultivation allowed ~?40 kg N ha^?1 to become available, but high DM and N yields (10.2–14.6 t DM ha^?1 and 405–544 kg N ha^?1) allowed ~?20 kg N ha^?1 to become available. Wetter weather in 2015 caused significantly more SMN losses than 2016 (20 kg N ha^?1 in 2015 and 5 kg N ha^?1 in 2016). The varieties Amos, Maro and Milvus lost significantly more SMN in the winter period, which may have been caused by more severe infection of Sclerotinia (these varieties were 50–80% more severely infected other varieties). Varietal effect was non-significant for winter losses in 2016, where no significant varietal differences in Sclerotinia infection were observed. 1 cut made ~?41 kg N ha^?1 available in the growing season of 2015, whilst 2 cut made significantly less (37 kg N ha^?1). Cutting was non-significant in 2016 but 1 cut was less susceptible to losses in the winter period. Cutting in 2015 did not significantly affect herbage DM and N yields in the first or second cut of 2016.     

The Association of Il28b Genotype with the Histological Features of Chronic Hepatitis C Is HCV Genotype Dependent

The interleukin 28B (IL28B) rs12979860 polymorphism is associated with treatment outcome in hepatitis C virus (HCV) genotype 1 and 4 patients. Its association with the histological features of chronic hepatitis C and disease severity needs further clarifications. To assess the correlation between IL28B genotype, HCV genotype and liver biopsy findings in untreated patients.

Materials and Methods

Pre-treatment liver biopsies from 335 HCV Caucasian patients (59% males, age 50 years) enrolled in the MIST study were staged for fibrosis and inflammation according to the METAVIR and the Ishak scoring systems; steatosis was dichotomized as <5% or ≥5%. IL28B was typed by Taqman Single Nucleotide Polymorphism (SNP) genotyping assay. HCV genotype was 1 in 151 (45%), 2 in 99 (30%), 3 in 50 (15%) and 4 in 35 (10%) patients. IL28B genotype was CC in 117 (34%), CT in 166 (49%) and TT in 52 (15%). At univariate analysis, the IL28B CC genotype was associated with severe portal inflammation in HCV-1 patients (CC vs. CT/TT: 86% vs. 63%, p = 0.005), severe lobular inflammation in HCV-2 patients (CC vs. CT/TT: 44% vs. 23%, p = 0.03), and less fatty infiltration in HCV-1 patients (CC vs. CT/TT: 72% vs. 51%, p = 0.02). Despite the lack of any association between IL28B and fibrosis stage, in HCV-3 patients IL28B CC correlated with METAVIR F3–F4 (CC vs. CT/TT: 74% vs. 26%, p = 0.05). At multivariate analysis, the genotype CC remained associated with severe portal inflammation in HCV-1, only (Odds Ratio (OR): 95% Confidence Interval (CI): 3.24 (1.23–8.51)). IL28B genotype is associated with the histological features of chronic hepatitis C in a HCV genotype dependent manner, with CC genotype being independently associated with severe portal inflammation.     

A Structure-Properties Relationship Study of Self-Healing Materials Based on Styrene and Furfuryl Methacrylate Cross-Linked via Diels–Alder Chemistry

A series of copolymers of styrene and furfuryl methacrylate characterized by various molecular structures (linear and star, block and random) is synthesized via atom transfer radical polymerization, and cross-linked with a bismaleimide by means of thermally reversible Diels–Alder (DA) reaction, to obtain self-healing materials. The prepared materials are studied in terms of gelation, swelling, thermal, and dynamic-mechanical analysis, with the aim of correlating relevant properties to their chemical structure. It is found that the furan/styrene ratio, as well as the molecular architecture, have a major influence on the properties. It is also found that the reversibility of the DA reaction is not complete in the solid state for materials with high cross-linking density. This study provides some important tools for the design of materials characterized by thermally reversible behavior, which find usually application as self-healing thermosets, coatings, or adhesives.     

Volume-Independent Sodium Toxicity in Peritoneal Dialysis: New Insights from Bench to Bed

Sodium overload is common in end-stage kidney disease (ESKD) and is associated with increased cardiovascular mortality that is traditionally considered a result of extracellular volume expansion. Recently, sodium storage was detected by Na23 magnetic resonance imaging in the interstitial tissue of the skin and other tissues. This amount of sodium is osmotically active, regulated by immune cells and the lymphatic system, escapes renal control, and, more importantly, is associated with salt-sensitive hypertension. In chronic kidney disease, the interstitial sodium storage increases as the glomerular filtration rate declines and is related to cardiovascular damage, regardless of the fluid overload. This sodium accumulation in the interstitial tissues becomes more significant in ESKD, especially in older and African American patients. The possible negative effects of interstitial sodium are still under study, though a higher sodium intake might induce abnormal structural and functional changes in the peritoneal wall. Interestingly, sodium stored in the interstial tissue is not unmodifiable, since it is removable by dialysis. Nevertheless, the sodium removal by peritoneal dialysis (PD) remains challenging, and new PD solutions are desirable. In this narrative review, we carried out an update on the pathophysiological mechanisms of volume-independent sodium toxicity and possible future strategies to improve sodium removal by PD.     

Non-Canonical Roles of Tau and Their Contribution to Synaptic Dysfunction

Tau plays a central role in a group of neurodegenerative disorders collectively named tauopathies. Despite the wide range of diverse symptoms at the onset and during the progression of the pathology, all tauopathies share two common hallmarks, namely the misfolding and aggregation of Tau protein and progressive synaptic dysfunctions. Tau aggregation correlates with cognitive decline and behavioural impairment. The mechanistic link between Tau misfolding and the synaptic dysfunction is still unknown, but this correlation is well established in the human brain and also in tauopathy mouse models. At the onset of the pathology, Tau undergoes post-translational modifications (PTMs) inducing the detachment from the cytoskeleton and its release in the cytoplasm as a soluble monomer. In this condition, the physiological enrichment in the axon is definitely disrupted, resulting in Tau relocalization in the cell soma and in dendrites. Subsequently, Tau aggregates into toxic oligomers and amyloidogenic forms that disrupt synaptic homeostasis and function, resulting in neuronal degeneration. The involvement of Tau in synaptic transmission alteration in tauopathies has been extensively reviewed. Here, we will focus on non-canonical Tau functions mediating synapse dysfunction.     

Dietary Fish Oil Alters DNA Methylation of Genes Involved in Polyunsaturated Fatty Acid Biosynthesis in Muscle and Liver of Atlantic Salmon (Salmo salar)

Adequate dietary supply of eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) is required to maintain health and growth of Atlantic salmon (Salmo salar). However, salmon can also convert α-linolenic acid (18:3n-3) into eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) by sequential desaturation and elongation reactions, which can be modified by 20:5n-3 and 22:6n-3 intake. In mammals, dietary 20:5n-3 + 22:6n-3 intake can modify Fads2 expression (Δ6 desaturase) via altered DNA methylation of its promoter. Decreasing dietary fish oil (FO) has been shown to increase Δ5fad expression in salmon liver. However, it is not known whether this is associated with changes in the DNA methylation of genes involved in polyunsaturated fatty acid synthesis. To address this, we investigated whether changing the proportions of dietary FO and vegetable oil altered the DNA methylation of Δ6fad_b, Δ5fad, Elovl2, and Elovl5_b promoters in liver and muscle from Atlantic salmon and whether any changes were associated with mRNA expression. Higher dietary FO content increased the proportions of 20:5n-3 and 22:6n-3 and decreased Δ6fad_b mRNA expression in liver, but there was no effect on Δ5fad, Elovl2, and Elovl5_b expression. There were significant differences between liver and skeletal muscle in the methylation of individual CpG loci in all four genes studied. Methylation of individual Δ6fad_b CpG loci was negatively related to its expression and to proportions of 20:5n-3 and 22:6n-3 in the liver. These findings suggest variations in dietary FO can induce gene-, CpG locus-, and tissue-related changes in DNA methylation in salmon.     

Dihydroartemisinin–Bile Acid Hybridization as an Effective Approach to Enhance Dihydroartemisinin Anticancer Activity

A series of hybrid compounds based on natural products—bile acids and dihydroartemisinin—were prepared by different synthetic methodologies and investigated for their in vitro biological activity against HL-60 leukemia and HepG2 hepatocellular carcinoma cell lines. Most of these hybrids presented significantly improved antiproliferative activities with respect to dihydroartemisinin and the parent bile acid. The two most potent hybrids of the series exhibited a 10.5- and 15.4-fold increase in cytotoxic activity respect to dihydroartemisinin alone in HL-60 and HepG2 cells, respectively. Strong evidence that an ursodeoxycholic acid hybrid induced apoptosis was obtained by flow cytometric analysis and western blot analysis.     

Glycidols Esters, 2-Chloropropane-1,3-Diols,and 3-Chloropropane-1,2-Diols Contents in Real Olive Oil Samples and their Relation with Diacylglycerols

A series of authentic virgin, refined, and mixtures of olive oils was analyzed for their content of 2-and 3-chloropropanediol (MCPD) esters expressed as 2−/3-MCPD, glycidol (and related glycidyl esters) (GE), and diglycerides (DAG). High concentrations of MCPD and GE were found, above all, in pomace oils, which come from the poorer starting raw materials, while virgin olive oils, as expected, do not contain any process contaminant. On the other hand, DAGs are present in all samples, demonstrating that their involvement in the formation of such contaminants only occurs when temperatures are higher than that used during the refining steps. The lack of correlation between the amounts of MCPD and GE can be ascribed to their completely different chemical stability as the epoxy ring of the GE opens easily, leading to both short-chain derivatives and/or MCPD itself. This finding can also explain the data about the absence of 2-MCPD in all the analyzed oil samples: other than the statistical probability and the steric effect of the SN2 formation mechanism, both in favor of the 3- derivative, we have also to consider the MCPD formation pathway involving glycidol that, under opportune conditions of refining, can increase the whole amount of 3-MCPD (under thermodynamic control, 3-MCPD is more stable).