SEC23B Loss-of-Function Suppresses Hepcidin Expression by Impairing Glycosylation Pathway in Human Hepatic Cells

Biallelic pathogenic variants in the SEC23B gene cause congenital dyserythropoietic anemia type II (CDA II), a rare hereditary disorder hallmarked by ineffective erythropoiesis, hemolysis, erythroblast morphological abnormalities, and hypo-glycosylation of some red blood cell membrane proteins. Abnormalities in SEC23B, which encodes the homonymous cytoplasmic COPII (coat protein complex II) component, disturb the endoplasmic reticulum to Golgi trafficking and affect different glycosylation pathways. The most harmful complication of CDA II is the severe iron overload. Within our case series (28 CDA II patients), approximately 36% of them exhibit severe iron overload despite mild degree of anemia and slightly increased levels of ERFE (the only erythroid regulator of hepcidin suppression). Thus, we hypothesized a direct role of SEC23B loss-of-function in the pathomechanism of hepatic iron overload. We established a hepatic cell line, HuH7, stably silenced for SEC23B. In silenced cells, we observed significant alterations of the iron status, due to both the alteration in BMP/SMADs pathway effectors and a reduced capability to sense BMP6 stimulus. We demonstrated that the loss-of-function of SEC23B is responsible of the impairment in glycosylation of the membrane proteins involved in the activation of the BMP/SMADs pathway with subsequent hepcidin suppression. Most of these data were confirmed in another hepatic cell line, HepG2, stably silenced for SEC23B. Our findings suggested that the pathogenic mechanism of iron overload in CDA II is associated to both ineffective erythropoiesis and to a specific involvement of SEC23B pathogenic variants at hepatic level. Finally, we demonstrated the ability of SEC23B paralog, i.e., SEC23A, to rescue the hepcidin suppression, highlighting the functional overlap between the two SEC23 paralogs in human hepatic cells.     

Molecularly imprinted polymers: present and future prospective

Molecular Imprinting Technology (MIT) is a technique to design artificial receptors with a predetermined selectivity and specificity for a given analyte, which can be used as ideal materials in various application fields. Molecularly Imprinted Polymers (MIPs), the polymeric matrices obtained using the imprinting technology, are robust molecular recognition elements able to mimic natural recognition entities, such as antibodies and biological receptors, useful to separate and analyze complicated samples such as biological fluids and environmental samples. The scope of this review is to provide a general overview on MIPs field discussing first general aspects in MIP preparation and then dealing with various application aspects. This review aims to outline the molecularly imprinted process and present a summary of principal application fields of molecularly imprinted polymers, focusing on chemical sensing, separation science, drug delivery and catalysis. Some significant aspects about preparation and application of the molecular imprinting polymers with examples taken from the recent literature will be discussed. Theoretical and experimental parameters for MIPs design in terms of the interaction between template and polymer functionalities will be considered and synthesis methods for the improvement of MIP recognition properties will also be presented.     

Cavitand-Based Coordination Cages: Achievements and Current Challenges

The research results obtained in the self-assembly of cavitand-based coordination cages are presented. Cavitands are ideal multidentate ligands for the creation of coordination cages due to their structural rigidity, concave structure, and great versatility in terms of synthetic modularity. The introduction of the ligand moieties on the resorcinarene building block proceeds at the upper rim of the cavity, to take full advantage of the structural rigidity of the cavitand scaffold. Two different synthetic strategies are employed for the formation of multidentate cavitand ligands: (a) functionalization at the apical positions and (b) introduction of the ligands as bridging units. The key features to control the cage self-assembly process emerging from this overview are the preorganization, for the cavitands, and kinetic versus thermodynamic stability of the resulting complexes, for the connecting metal. The versatility of this class of coordination cages is demonstrated by the formation of their heterotopic and heteronuclear versions, as well as their self-assembly on gold and silicon surfaces. Desymmetrization of the cages is appealing because of the resulting differentiation of the inner cavities in terms of shape and interactivity, while surface self-assembly represents an important opportunity to expand the application range of these objects.     

Differential scanning calorimetry analysis of an enhanced LiNi0.8Co0.2O2 cathode with single wall carbon nanotube conductive additives

The replacement of traditional conductive carbon additives with single wall carbon nanotubes (SWCNTs) in lithium metal oxide cathode composites has been shown to enhance thermal stability as well as power capability and electrode energy density. The dispersion of 1 wt% high purity laser-produced SWCNTs in a LiNi_0.8Co_0.2O₂ electrode created an improved percolation network over an equivalent composite electrode using 4 wt% Super C65 carbon black; evidenced by additive connectivity in SEM images and an order of magnitude increase in electrode electrical conductivity. The cathode with 1 wt% SWCNT additives showed comparable active material capacity (185–188 mAh g⁻¹), at a low rate, and Coulombic efficiency to the cathode composite with 4 wt% Super C65. At increased cycling rates, the cathode with SWCNT additives had higher capacity retention with more than three times the capacity at 10C (16.4 mA cm⁻²). The thermal stability of the electrodes was evaluated by differential scanning calorimetry after charging to 4.3 V and float charging for 12 h. A 40% reduction of the cathode exothermic energy released was measured when using 1 wt% SWCNTs as the additive. Thus, the results demonstrate that replacing traditional conductive carbon additives with a lower weight loading of SWCNTs is a simple way to improve the thermal transport, safety, power, and energy characteristics of cathode composites for lithium ion batteries.     

Preparation,structure, and properties of montmorillonite/cellulose II/natural rubber nanocomposites

In this work, sodium montmorillonite clay was added, as filler, to nanocomposites of natural rubber (NR) and cellulose II (regenerated cellulose) in amounts varying from 0 to 5 phr (per hundred resin). Natural rubber (NR)/cellulose II/montmorillonite nanocomposites were prepared by co‐coagulating NR latex, montmorillonite aqueous suspension and cellulose xanthate. The clay was previously exfoliated in water, and the resulting suspension was then added to the mixture of NR latex with cellulose xanthate. Morphological, rheometric, mechanical, and dynamic mechanical properties were evaluated, and an increase in these properties was observed upon the addition of cellulose and clay nanomaterials to the rubber matrix. The results show the advantage in using cellulose as a nanopolymer as well as MMT as nanofiller. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Impact of microwave synthesis conditions on the rechargeable capacity of LiCoPO4 for lithium ion batteries

Lithium transition metal phosphates have the capability of improving cathode energy densities up to 800 Wh kg^?1, a 27 % increase over conventional cathode active material energy densities. In this study, the effect of base-to-acid (NH₄OH:H₃PO₄) stoichiometric conditions on the intrinsic reversible capacity of lithium cobalt phosphate (LiCoPO₄) active material are investigated through microwave synthesis and electrochemical testing. Variation in solution pH results in an increase of 69 mAh g^?1 in achievable capacity. X-ray diffraction results show highly crystalline LiCoPO₄, with particle sizes ranging from 200 nm to greater than 1 μm based upon scanning electron microscopy. Electrochemical analysis with 1 M LiPF₆ EC:EMC (1:2 v/v) provides the highest capacity over multiple cycles. A discharge capacity of 128 mAh g^?1 (78 % of theoretical capacity) is achievable for intrinsic LiCoPO₄ without further treatment (e.g., carbon coating) at an effective 0.1 C rate with a proper constant current–constant voltage step. Analysis of reported synthesis techniques shows that microwave synthesis yields the highest capacity for the intrinsic LiCoPO₄ material to date.     

Hybrid MCM-41 grafted by a general microwave-assisted procedure: a characterization study

Hybrid materials obtained through a Microwave-assisted grafting of organic functional groups on mesoporous silica (MCM-41 type) have been characterized by X-ray powder diffraction, TG-DSC, N₂ adsorption, solid state ¹³C- and ²⁹Si-NMR, TEM and SEM. The studied grafting procedure is effective in the preparation of hybrid organosilicas under solvent-free conditions. Microwaves allows an ultra-fast and clean functionalization of the mesoporous materials and the method has been applied to produce a wide series of functional materials. The hybrid materials maintain the original mesoporous structure when the loading of linked organic groups does not exceed 10 %. In this cases, the slight pore volume reduction is linearly correlated to the organic amount in the product. If functional groups able to interact among them through hydrogen bond are used, hybrid materials exhibit high Organic/SiO₂ ratios and low pore volumes due to the formation of a network occluding the pores, where functional groups of free organosilane molecules interacts with the functional groups of molecules linked to the matrix. NMR data confirm that the network is composed by organosilane molecules linked or not to the framework. Acid washing is able to labilize hydrogen bond and open the network. In the case of bulky but chemically inert functionalising agents the network is not produced.     

Calcium phosphate incorporated poly(ethylene oxide)‐based nanocomposite electrolytes for lithium batteries. I. Ionic conductivity and positron annihilation lifetime spectroscopy studies

Nanocomposite polymer electrolytes (NCPEs) composed of poly(ethylene oxide), calcium phosphate [Ca₃(PO₄)₂], and lithium perchlorate (LiClO₄)/lithium bis(trifluoromethane sulfonyl)imide [LiN(CF₃SO₂)₂ or LiTFSI] in various proportions were prepared by a hot‐press method. The membranes were characterized by scanning electron microscopy, differential scanning calorimetry, thermogravimetry–differential thermal analysis, ionic conductivity testing, and transference number studies. The free volume of the membranes was probed by positron annihilation lifetime spectroscopy at 30°C, and the results supported the ionic conductivity data. The NCPEs with LiClO₄ exhibited higher ionic conductivities than the NCPE with LiTFSI as a salt. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Peptidyl Vinyl Ketone Irreversible Inhibitors of Rhodesain: Modifications of the P2 Fragment

In this paper, we report the design, synthesis and biological investigation of a series of peptidyl vinyl ketones obtained by modifying the P2 fragment of previously reported highly potent inhibitors of rhodesain, the main cysteine protease of Trypanosoma brucei rhodesiense. Investigation of the structure–activity relationship led us to identify new rhodesain inhibitors endowed with an improved selectivity profile (a selectivity index of up to 22 000 towards the target enzyme), and/or an improved antitrypanosomal activity in the sub-micromolar range.