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.     

Discovery of Ubonodin,an Antimicrobial Lasso Peptide Active against Members of the Burkholderia cepacia Complex

We report the heterologous expression, structure, and antimicrobial activity of a lasso peptide, ubonodin, encoded in the genome of Burkholderia ubonensis. The topology of ubonodin is unprecedented amongst lasso peptides, with 18 of its 28 amino acids found in the mechanically bonded loop segment. Ubonodin inhibits RNA polymerase in vitro and has potent antimicrobial activity against several pathogenic members of the Burkholderia genus, most notably B. cepacia and B. multivorans, causative agents of lung infections in cystic fibrosis patients.     

化学合成制药综合废水的处理

本文介绍了化学合成制药废水的处理工艺、原理和运行效果,该工艺处理后的污水完全达到国家规定的污水排放标准。     

Scaling up effects of Mg hydride in a temperature and pressure-controlled hydrogen storage device

A research program addressed to evaluate the magnesium hydride storage scaling up effects is being developed by CESI RICERCA, Milano, and the Hydrogen Group of Padova University. A storage device containing 500 g of magnesium hydride powder (manufactured by Venezia Tecnologie S.p.A. using high-energy ball milling) has been designed and tested in different operating conditions. A number of absorption and desorption cycles at different temperatures and pressures has been carried out in order to see if the results are comparable with laboratory data obtained on small amounts (fractions of grams) of powder samples. A sensible performance degradation that reduced the overall storage capacity of about 50% has been noticed after 20 cycles, presumably due to local powder heating, fragmentation and subsequent compaction. Further tests on a smaller tank equipped also with a porous baffle gave useful indications for the design of an improved large hydrogen reservoir.     

β-Cyclodextrin Inclusion Complex to Improve Physicochemical Properties of Pipemidic Acid: Characterization and Bioactivity Evaluation

The aptitude of cyclodextrins (CDs) to form host-guest complexes has prompted an increase in the development of new drug formulations. In this study, the inclusion complexes of pipemidic acid (HPPA), a therapeutic agent for urinary tract infections, with native β-CD were prepared in solid state by kneading method and confirmed by FT-IR and ¹H NMR. The inclusion complex formation was also characterized in aqueous solution at different pH via UV-Vis titration and phase solubility studies obtaining the stability constant. The 1:1 stoichiometry was established by a Job plot and the inclusion mechanism was clarified using docking experiments. Finally, the antibacterial activity of HPPA and its inclusion complex was tested on P. aeruginosa, E. coli and S. aureus to determine the respective EC_50s and EC_90s. The results showed that the antibacterial activity of HPPA:β-CD against E. coli and S. aureus is higher than that of HPPA. Furthermore, HPPA and HPPA:β-CD, tested on human hepatoblastoma HepG2 and MCF-7 cell lines by MTT assay, exhibited, for the first time, antitumor activities, and the complex revealed a higher activity than that of HPPA. The use of β-CD allows an increase in the aqueous solubility of the drug, its bioavailability and then its bioactivity.     

Tunable frequency-selective surfaces for beam-steering applications

First results from a study on tunable frequency-selective surfaces (FSSs) used for beam-steering applications are reported. In particular, the scattering response of a multilayer passband FSS based on varactorloaded rectangular slots has been investigated. Simulated and measured results show that tunable FSSs can be employed to locally control the phase of the transmitted field with limited amplitude losses.     

Persistent organic pollutants in farmed European sea bass (Dicentrarchus labrax,Linnaeus, 1758) from Sicily (Italy)

Farmed European sea bass (Dicentrarchus labrax, Linnaeus, 1758) were collected during 2016 from one Sicilian fish farm that uses two different rearing systems – sea cage and concrete tank – for determination of polychlorinated biphenyls (PCB), organochlorine pesticides (OCP) and polycyclic aromatic hydrocarbons (PAH) residues by HRGC-MS/MS. Moreover, commercial feed was analysed. This study aimed to determine whether the different rearing systems affect the concentration of these compounds, and to assess the safety of cultured fish. PCBs represent the pollutants with the highest concentration; in particular, PCB138 and 153 have the highest concentration in almost all samples. Among OCPs, only 4,4′-DDE, 4,4′-DDD and 4,4′-DDT residues have been detected. Concerning PAHs, only fluorene and phenanthrene were detected, in both rearing systems. Although some residues of organic pollutants were found in the analysed samples, they were always below the MRLs, so the results suggest that farmed sea bass are safe for human consumption.     

Numerical simulation of turbulent gas flames in tubes

Computational fluid dynamics (CFD) is an emerging technique to predict possible consequences of gas explosion and it is often considered a powerful and accurate tool to obtain detailed results. However, systematic analyses of the reliability of this approach to real-scale industrial configurations are still needed. Furthermore, few experimental data are available for comparison and validation.In this work, a set of well documented experimental data related to the flame acceleration obtained within obstacle-filled tubes filled with flammable gas-air mixtures, has been simulated. In these experiments, terminal steady flame speeds corresponding to different propagation regimes were observed, thus, allowing a clear and prompt characterisation of the numerical results with respect to numerical parameters, as grid definition, geometrical parameters, as blockage ratio and to mixture parameters, as mixture reactivity.The CFD code AutoReagas was used for the simulations. Numerical predictions were compared with available experimental data and some insights into the code accuracy were determined. Computational results are satisfactory for the relatively slower turbulent deflagration regimes and became fair when choking regime is observed, whereas transition to quasi-detonation or Chapman-Jogouet (CJ) were never predicted.     

Crossover enhancements in GEFREX

This letter describes some improvements to the crossover operator in the genetic-neuro-fuzzy algorithm called genetic fuzzy rule extractor (GEFREX). Although, the new crossovers studied are very simple, the performance of GEFREX, in terms of learning time, is decidedly improved.