Na-feldspar (F) and kaolinite (K) system at high temperature: Resulting phase composition,micro-structural features and mullite-glass Gibbs energy of formation,as a function of F/K ratio and kaolinite crystallinity

The system Na-feldspar (F) and kaolinite (K) was investigated at temperatures of interest in ceramic applications (1200–1280 °C) to study the effects of F/K ratios by weight and crystallinity degree of kaolinite on the final product, micro-structural features and mullite-glass Gibbs energy of formation (ΔG^eff). Mullite and glass are the dominant phases; in general, the higher the temperature, the larger the former. An F/K increase promotes the formation of glass and secondary mullite, appearing along with the primary one. ΔG^eff was modelled by α(T) × (F/K)² + β(T) × F/K + γ(T), α, β and γ being linear functions of temperature whose coefficients were determined by fitting the ΔG^eff-theoretical to the ΔG^eff-obtained from the measured phase compositions. ΔG^eff is less affected by temperature than by F/K, whose increase shifts equilibrium towards glass phases. The ΔG^eff-curves for ordered and disordered kaolinite intersect one another at F/K ～0.5, a ratio close to that used in industrial practice.     

Pullulan: A versatile coating agent for superparamagnetic iron oxide nanoparticles

Ultrasmall superparamagnetic iron oxide (Fe₃O₄) nanoparticles coated by biocompatible pullulan (Pu‐USPIO) with sizes below 10 nm and having a magnetite core and a hydrophilic outer shell of pullulan were prepared. The formed Pu‐USPIOs were thoroughly characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, atomic force microscopy, and small‐angle X‐ray scattering experiments. The content of magnetic nanoparticles embedded into the pullulan matrix was determined by thermogravimetric analysis. Vibrating sample magnetometry analysis was used to evaluate the magnetic properties of the Pu‐USPIO samples. Because of the presence of pullulan, these nanoparticles could be conditioned in many versatile forms, from a clear solution to magnetic films, for potential applications, including magnetic hyperthermia mediators. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42926.     

The L467F-F508del Complex Allele Hampers Pharmacological Rescue of Mutant CFTR by Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis Patients: The Value of the Ex Vivo Nasal Epithelial Model to Address Non-Responders to CFTR-Modulating Drugs

Loss-of-function mutations of the CFTR gene cause cystic fibrosis (CF) through a variety of molecular mechanisms involving altered expression, trafficking, and/or activity of the CFTR chloride channel. The most frequent mutation among CF patients, F508del, causes multiple defects that can be, however, overcome by a combination of three pharmacological agents that improve CFTR channel trafficking and gating, namely, elexacaftor, tezacaftor, and ivacaftor. This study was prompted by the evidence of two CF patients, compound heterozygous for F508del and a minimal function variant, who failed to obtain any beneficial effects following treatment with the triple drug combination. Functional studies on nasal epithelia generated in vitro from these patients confirmed the lack of response to pharmacological treatment. Molecular characterization highlighted the presence of an additional amino acid substitution, L467F, in cis with the F508del variant, demonstrating that both patients were carriers of a complex allele. Functional and biochemical assays in heterologous expression systems demonstrated that the double mutant L467F-F508del has a severely reduced activity, with negligible rescue by CFTR modulators. While further studies are needed to investigate the actual prevalence of the L467F-F508del allele, our results suggest that this complex allele should be taken into consideration as plausible cause in CF patients not responding to CFTR modulators.     

Combined monte carlo/thermodynamic model of formation of microporous aggregate structure like silica from quaternary ammonium silicate solutions

Quaternary ammonium silicate is a surfactant with very high content of silica that allows its use for preparation of protective coatings. The problem of silica aggregation from quaternary ammonium solution in limited volume is the focus of this paper. The system is described by a model based on a Monte Carbo approach with thermodynamic limitations. Thermodynamic characteristics are estimated by statistical polymer method. The model is employed for estimation of such properties as monomer concentration and tortuosity. The results of computer simulation are used for forecasting properties of coatings and for practical preparation of samples coated with quaternary ammonium silicate-based composition.     

CHID1 Is a Novel Prognostic Marker of Non-Small Cell Lung Cancer

There is an urgent need for identification of new prognostic markers and therapeutic targets for non-small cell lung cancer (NSCLC). In this study, we evaluated immune cells markers in 100 NSCLC specimens. Immunohistochemical analysis revealed no prognostic value for the markers studied, except CD163 and CD206. At the same time, macrophage markers iNOS and CHID1 were found to be expressed in tumor cells and associated with prognosis. We showed that high iNOS expression is a marker of favorable prognosis for squamous cell lung carcinoma (SCC), and NSCLC in general. Similarly, high CHID1 expression is a marker of good prognosis in adenocarcinoma and in NSCLC in general. Analysis of prognostic significance of a high CHID1/iNOS expression combination showed favorable prognosis with 20 months overall survival of patients from the low CHID1/iNOS expression group. For the first time, we demonstrated that CHID1 can be expressed by NSCLC cells and its high expression is a marker of good prognosis for adenocarcinoma and NSCLC in general. At the same time, high expression of iNOS in tumor cells is a marker of good prognosis in SCC. When used in combination, CHID1 and iNOS show a very good prognostic capacity for NSCLC. We suggest that in the case of lung cancer, tumor-associated macrophages are likely ineffective as a therapeutic target. At the same time, macrophage markers expressed by tumor cells may be considered as targets for anti-tumor therapy or, as in the case of CHID1, as potential anti-tumor agents.     

Prenatal THC Does Not Affect Female Mesolimbic Dopaminergic System in Preadolescent Rats

Cannabis use among pregnant women is increasing worldwide along with permissive sociocultural attitudes toward it. Prenatal cannabis exposure (PCE), however, is associated with adverse outcome among offspring, ranging from reduced birth weight to child psychopathology. We have previously shown that male rat offspring prenatally exposed to Δ9-tetrahydrocannabinol (THC), a rat model of PCE, exhibit extensive molecular, cellular, and synaptic changes in dopamine neurons of the ventral tegmental area (VTA), resulting in a susceptible mesolimbic dopamine system associated with a psychotic-like endophenotype. This phenotype only reveals itself upon a single exposure to THC in males but not females. Here, we characterized the impact of PCE on female behaviors and mesolimbic dopamine system function by combining in vivo single-unit extracellular recordings in anesthetized animals and ex vivo patch clamp recordings, along with neurochemical and behavioral analyses. We find that PCE female offspring do not show any spontaneous or THC-induced behavioral disease-relevant phenotypes. The THC-induced increase in dopamine levels in nucleus accumbens was reduced in PCE female offspring, even when VTA dopamine activity in vivo and ex vivo did not differ compared to control. These findings indicate that PCE impacts mesolimbic dopamine function and its related behavioral domains in a sex-dependent manner and warrant further investigations to decipher the mechanisms determining this sex-related protective effect from intrauterine THC exposure.     

Complementary Effects of Carbamylated and Citrullinated LL37 in Autoimmunity and Inflammation in Systemic Lupus Erythematosus

LL37 acts as T-cell/B-cell autoantigen in Systemic lupus erythematosus (SLE) and psoriatic disease. Moreover, when bound to “self” nucleic acids, LL37 acts as “danger signal,” leading to type I interferon (IFN-I)/pro-inflammatory factors production. T-cell epitopes derived from citrullinated-LL37 act as better antigens than unmodified LL37 epitopes in SLE, at least in selected HLA-backgrounds, included the SLE-associated HLA-DRB1*1501/HLA-DRB5*0101 backgrounds. Remarkably, while “fully-citrullinated” LL37 acts as better T-cell-stimulator, it loses DNA-binding ability and the associated “adjuvant-like” properties. Since LL37 undergoes a further irreversible post-translational modification, carbamylation and antibodies to carbamylated self-proteins other than LL37 are present in SLE, here we addressed the involvement of carbamylated-LL37 in autoimmunity and inflammation in SLE. We detected carbamylated-LL37 in SLE-affected tissues. Most importantly, carbamylated-LL37-specific antibodies and CD4 T-cells circulate in SLE and both correlate with disease activity. In contrast to “fully citrullinated-LL37,” “fully carbamylated-LL37” maintains both innate and adaptive immune-cells’ stimulatory abilities: in complex with DNA, carbamylated-LL37 stimulates plasmacytoid dendritic cell IFN-α production and B-cell maturation into plasma cells. Thus, we report a further example of how different post-translational modifications of a self-antigen exert complementary effects that sustain autoimmunity and inflammation, respectively. These data also show that T/B-cell responses to carbamylated-LL37 represent novel SLE disease biomarkers.