Regulation of type I interferons in health and autoimmune disease

Type I interferons (IFN) have a crucial role in the pathogenesis of a range of autoimmune diseases including systemic lupus erythematosus (SLE). Increased IFN activity is observed at preclinical stages and associated with disease progression, but the cause of this dysregulation remains unclear. Plasmacytoid dendritic cells (pDCs) produce large amounts of IFNs in viral infection, however their precise role in autoimmunity is still elusive. Peripheral blood and skin biopsies from different patient groups were used for gene expression assays, immunophenotyping, in vitro functional assays, transcriptomics and other assays to investigate the dysregulated IFN axis and the role of pDCs in preclinical autoimmunity and SLE. In preclinical autoimmunity and SLE, pDCs were found to exhibit an exhausted phenotype with: (i) loss of TLR-mediated IFN-α production; (ii) failure to induce T cell activation; (iii) transcriptional profile of cellular senescence; (iv) increased telomere erosion. In contrast, diffuse expression of type I IFNs was observed in the epidermis but not in leucocyte-infiltrating areas of patients with SLE as well as in non-lesional skin of individuals with preclinical autoimmunity. Additionally, keratinocytes isolated from non-lesional skin of patients with SLE and individuals with preclinical autoimmunity showed a significantly enhanced type I IFN expression in response to UV light and nucleic acids. Lastly, TNF-α regulates the function of pDCs by suppressing IFN-α production but enhancing a functional drift to antigen presentation and T cell activation. These findings revise our understanding of immune regulation in human autoimmunity. Non-haematopoietic tissue cells can perpetuate IFN responses; meanwhile the professional IFN-producing pDCs have lost their immunogenic properties. In patients with SLE, these insights may indicate potential therapeutic targets outside the conventional immune system, while knowledge of how IFN dysregulation initiates could allow disease prevention

Management and treatment of children, young people and adults with systemic lupus erythematosus: British Society for Rheumatology guideline scope

Lay Summary: Systemic lupus erythematosus (SLE) is a lifelong condition in which the immune system damages the body’s own tissues, causing various symptoms including rashes, hair loss, mouth ulcers, joint pain and overwhelming tiredness. It can also affect major organs including the kidneys, heart, lungs and brain. SLE can present during childhood, but most commonly affects young and middle-aged females. It is approximately nine times more common in females than males. The disease can lead to disability, poor quality of life and even death in severe cases. Treatments can often be difficult to tolerate and can cause both short- and long-term side effects. Guidelines developed by the British Society for Rheumatology aim to provide guidance for diagnosing and treating people with SLE. This is necessary to ensure that the most up-to-date approach is followed, utilising the safest and most effective treatments. This article describes the plan for a guideline in SLE that is being updated to cover new evidence that has been published since 2017 relating to the treatment and management of SLE. The guideline will take a whole life course approach, from childhood to adulthood, and is being undertaken by a working group consisting of paediatric and adult rheumatologists and nephrologists, SLE experts, general practitioners, specialist nurses and other healthcare professionals, together with people with SLE and representatives from patient organizations. The guideline will be developed using the methods and processes outlined in the British Society for Rheumatology document ‘Creating Clinical Guidelines: Our Protocol’

Study of fluid catalytic cracking catalysts deactivation due to heavy metals deposition

Taking into account both the worldwide energy crisis and the drastic increase in the demand for lighter hydrocarbon fractions such as gasoline and diesel, the refineries are forced to upgrade more and more of heavier or resid fractions into lighter products via catalytic cracking. However, the residual cracking poses numerous problems for the oil companies and the catalyst manufacturers. The increasing portion of large molecules containing hetero-atoms and metal contaminants in fractions of increasing boiling point mainly accounts for the difficulties in processing heavy oils. With the residuum fluid catalytic cracking (RFCC) operating conditions, almost 100% of these metals deposit on the catalyst surface, consequently decreasing catalyst’s stability, activity and selectivity, thus demanding new FCC catalyst technologies. Due to the complexity of the deactivation mechanisms, the prediction of the commercial FCC catalyst performance is one of the most important research activities in the oil refining industry. The main scope of the present study was to investigate the factors that affect the metal related deactivation of the FCC catalysts in order to optimize the simulation of the real deactivation by the laboratory deactivation methods.Τόσο η παγκόσμια ενεργειακή κρίση, όσο και η μεγάλη αύξηση στη ζήτηση των ελαφριών προϊόντων διυλιστηρίου, όπως η βενζίνη και το ντίζελ, υποδεικνύουν την αναβάθμιση βαρέων κλασμάτων πετρελαίου προς ελαφρύτερα κλάσματα υψηλότερης αξίας μέσω της διεργασίας καταλυτικής πυρόλυσης (FCC: Fluid Catalytic Cracking). Ωστόσο η επεξεργασία τέτοιων τροφοδοσιών δημιουργεί λειτουργικά προβλήματα τόσο στη μονάδα όσο και στον χρησιμοποιούμενο καταλύτη FCC λόγω της αυξημένης συγκέντρωσης ετεροατόμων και δηλητηριωδών μετάλλων (Ni, V). Σε συνθήκες καταλυτικής πυρόλυσης Βαρέων Τροφοδοσιών (RFCC: Residuum Fluid Catalytic Cracking) σχεδόν 100% των δηλητηριωδών μετάλλων εναποτίθενται στον καταλύτη, ελαττώνοντας σημαντικά τη σταθερότητα, την ενεργότητα και την εκλεκτικότητα του. Λόγω της πολυπλοκότητας του μηχανισμού απενεργοποίησης, η πρόβλεψη της απόδοσης εμπορικών καταλυτών από μονάδες εργαστηριακής κλίμακας εξακολουθεί να παρουσιάζει μεγάλο ερευνητικό ενδιαφέρον. Βασικό στόχο της παρούσας διατριβής αποτέλεσε η διερεύνηση των παραγόντων που επηρεάζουν την απενεργοποίηση του καταλύτη FCC από τα δηλητηριώδη μέταλλα (Ni, V), ώστε να βελτιστοποιηθεί η προσομοιωτική ικανότητα των εργαστηριακών μεθόδων απενεργοποίησης. […

Effect of Steam Deactivation Severity of ZSM-5 Additives on LPG Olefins Production in the FCC Process

ZSM-5-containing catalytic additives are widely used in oil refineries to boost light olefin production and improve gasoline octanes in the Fluid Catalytic Cracking (FCC) process. Under the hydrothermal conditions present in the FCC regenerator (typically >700 °C and >8% steam), FCC catalysts and additives are subject to deactivation. Zeolites (e.g., Rare Earth USY in the base catalyst and ZSM-5 in Olefins boosting additives) are prone to dealumination and partial structural collapse, thereby losing activity, micropore surface area, and undergoing changes in selectivity. Fresh catalyst and additives are added at appropriate respective levels to the FCC unit on a daily basis to maintain overall targeted steady-state (equilibrated) activity and selectivity. To mimic this process under accelerated laboratory conditions, a commercial P/ZSM-5 additive was hydrothermally equilibrated via a steaming process at two temperatures: 788 °C and 815 °C to simulate moderate and more severe equilibration industrial conditions, respectively. n-Dodecane was used as probe molecule and feed for micro-activity cracking testing at 560 °C to determine the activity and product selectivity of fresh and equilibrated P-doped ZSM-5 additives. The fresh/calcined P/ZSM-5 additive was very active in C12 cracking while steaming limited its activity, i.e., at catalyst-to-feed (C/F) ratio of 1, about 70% and 30% conversion was obtained with the fresh and steamed additives, respectively. A greater activity drop was observed upon increasing the hydrothermal deactivation severity due to gradual decrease of total acidity and microporosity of the additives. However, this change in severity did not result in any selectivity changes for the LPG (liquefied petroleum gas) olefins as the nature (Brønsted-to-Lewis ratio) of the acid/active sites was not significantly altered upon steaming. Steam deactivation of ZSM-5 had also no significant effect on aromatics formation which was enhanced at higher conversion levels. Coke remained low with both fresh and steam-deactivated P/ZSM-5 additives

Erratum: Effect of alkali (Cs) doping on the surface chemistry and CO2hydrogenation performance of CuO/CeO2catalysts [Journal of CO2 Utilization (2021) 44 (101408) DOI: 10.1016/j.jcou.2020.101408)

The publisher regrets that the printed version of the above article contained a number of typo errors inserted during proofing process. The publisher would like to apologise for any inconvenience caused. In particular: • The units throughout the text must be in the form A/B instead of A/ B-1, i.e., cm3/min, °C/min, μmol/g, gcat/m3, mol/m3, m2/s instead of cm3/min-1, °C/min-1, μmol/g-1, gcat/m-3, mol/m-3, m2/s-1, respectively. • In the definition of turnover frequency (Eq. (6)) the term B must be defined as the total CO2uptake in μmol/g, i.e. "⋯derived by the total CO2uptake in μmol/g (B) calculated by CO2-TPD measurements" instead of "⋯derived by the total CO2uptake in 40 μmol/g (B) calculated by CO2-TPD measurements". • The y-axis in Figure 7 must be dimensionless, i.e., ln(TOF) instead of ln(TOF) (s-1).publishersversionpublishe

Type I Interferon-Mediated Autoimmune Diseases: pathogenesis, diagnosis, and targeted therapy

Type I interferons (IFN-I) are a group of molecules with pleiotropic effects on the immune system forming a crucial link between innate and adaptive immune responses. Apart from their important role in antiviral immunity, IFN-I are increasingly recognized as key players in autoimmune connective tissue diseases such as systemic lupus erythematosus (SLE). Novel therapies that target IFN-I appear effective in SLE in early trials, but effectiveness is related to the presence of IFN-I biomarkers. IFN-I biomarkers may also act as positive or negative predictors of response to other biologics. Despite the high failure rate of clinical trials in SLE, subgroups of patients often respond better. Fully optimizing the potential of these agents is therefore likely to require stratification of patients using IFN-I biomarkers. This suggests the unified concept of Type I Interferon Mediated Autoimmune Diseases, as a grouping including patients with a variety of different traditional diagnoses

Effect of alkali (Cs) doping on the surface chemistry and CO2 hydrogenation performance of CuO/CeO2 catalysts

Summarization: The reaction of captured carbon dioxide with renewable hydrogen towards the eventual indirect production of liquid hydrocarbons via CO2 reduction to CO (reverse water-gas shift reaction, rWGS) is a promising pathway in the general scheme of worldwide CO2 valorization. Copper-ceria oxides have been largely employed as rWGS catalysts owing to their unique properties linked to copper-ceria interactions. Here, we report on the fine-tuning of CuO/CeO2 composites by means of alkali promotion. In particular, this work aims at exploring the effect of cesium doping (0–4 atoms Cs per nm2) on co-precipitated CuO/CeO2 catalysts under CO2 hydrogenation conditions. The as-prepared samples were characterized by N2 physisorption, X-ray diffraction (XRD), H2-temperature programmed reduction (H2-TPR), X-ray photoelectron spectroscopy (XPS), CO2-temperature programmed desorption (CO2-TPD), Fourier-transform infrared spectroscopy (FTIR) of pyridine adsorption and CO-diffuse reflectance Fourier-transform infrared spectroscopy (CO-DRIFTS). The results demonstrated that a low amount of Cs exerted a beneficial effect on CO selectivity, inhibiting, however, CO2 conversion. Specifically, a doping of 2 atoms Cs per nm2 offers > 96 % CO selectivity and equilibrium CO2 conversion at temperatures as low as 430 °C, whereas further increase in cesium loading had no additional impact. The present findings can be mainly interpreted on a basis of the alkali effect on the textural and acid/base properties; Cs doping results in a significant reduction of the surface area and thus to a lower population of active sites for CO2 conversion, whereas it enhances the formation of basic sites and the stabilization of partially reduced Cu+ species, favoring CO selectivity.Presented on: Journal of Co2 Utilizatio

Erratum to “Effect of alkali (Cs) doping on the surface chemistry and CO2 hydrogenation performance of CuO/CeO2 catalysts” [J. CO2 Util. 44 (2021) 101408]

Summarization: Correction to "Effect of alkali (Cs) doping on the surface chemistry and CO2 hydrogenation performance of CuO/CeO2 catalysts" article, published at Journal of CO2 Utilization, vol 44, February 2021.Presented on

Management and treatment of children, young people and adults with systemic lupus erythematosus: British Society for Rheumatology guideline scope.

Funder: British Society for Rheumatology; DOI: https://doi.org/10.13039/501100000568The objective of this guideline is to provide up-to-date, evidence-based recommendations for the management of SLE that builds upon the existing treatment guideline for adults living with SLE published in 2017. This will incorporate advances in the assessment, diagnosis, monitoring, non-pharmacological and pharmacological management of SLE. General approaches to management as well as organ-specific treatment, including lupus nephritis and cutaneous lupus, will be covered. This will be the first guideline in SLE using a whole life course approach from childhood through adolescence and adulthood. The guideline will be developed with people with SLE as an important target audience in addition to healthcare professionals. It will include guidance related to emerging approved therapies and account for National Institute for Health and Care Excellence Technology Appraisals, National Health Service England clinical commissioning policies and national guidance relevant to SLE. The guideline will be developed using the methods and rigorous processes outlined in 'Creating Clinical Guidelines: Our Protocol' by the British Society for Rheumatology