Type III interferons induce pyroptosis in gut epithelial cells and impair mucosal repair.

Tissue damage and repair are hallmarks of inflammation. Despite a wealth of information on the mechanisms that govern tissue damage, mechanistic insight into how inflammation affects repair is lacking. Here, we investigated how interferons influence tissue repair after damage to the intestinal mucosa.

Harnessing the Vnn1 pantetheinase pathway boosts short chain fatty acids production and mucosal protection in colitis.

Objective: In the management of patients with IBD, there is a need to identify prognostic markers and druggable biological pathways to improve mucosal repair and probe the efficacy of tumour necrosis factor alpha biologics. Vnn1 is a pantetheinase that degrades pantetheine to pantothenate (vitamin B, a precursor of coenzyme A (CoA) biosynthesis) and cysteamine. Vnn1 is overexpressed by inflamed colonocytes.

What are the Unmet Needs and Most Relevant Treatment Outcomes According to Patients with Inflammatory Bowel Disease? A Qualitative Patient Preference Study.

Background And Aims: As more therapeutic options with their own characteristics become available for inflammatory bowel disease [IBD], drug development and individual treatment decision-making needs to be tailored towards patients' preferences and needs. This study aimed to understand patient preferences among IBD patients, and their most important treatment outcomes and unmet needs.

Methods: This qualitative study consisted of [1] a scoping literature review, [2] two focus group discussions [FGDs] with IBD patients [n = 11] using the nominal group technique, and [3] two expert panel discussions.

Zinc-dependent histone deacetylases drive neutrophil extracellular trap formation and potentiate local and systemic inflammation.

Neutrophil extracellular traps (NETs) have been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS) driven by viruses or bacteria, as well as in numerous immune-mediated disorders. Histone citrullination by the enzyme peptidylarginine deiminase 4 (PAD4) and the consequent decondensation of chromatin are hallmarks in the induction of NETs. Nevertheless, additional histone modifications that may govern NETosis are largely overlooked.

Cardiovascular prognosis in patients admitted to an emergency department with hypertensive emergencies and urgencies.

Background: At present, few data are available on the prognosis of hypertensive emergencies and urgencies admitted to emergency departments.

Aim: The aim of our study was to evaluate the incidence of total and cardiovascular events during follow-up in hypertensive patients admitted to the emergency departments of Brescia Hospital (Northern Italy) with hypertensive emergencies or urgencies from 1 January to 31 December 2015.

Methods: Medical records of patients aged more than 18 years, admitted to the emergency department with SBP values at least 180 mmHg (SBP) and/or DBP values at least 120 mmHg (DBP) were collected and analysed (18% of patients were classified as 'hypertensive emergency' and 82% as 'hypertensive urgency').

Pediatric Mandibular Reconstruction Using the Vascularized Fibula Free Flap: Functional Outcomes in 34 Consecutive Patients.

Background: The vascularized fibula free flap is a workhorse flap in pediatric mandibular reconstruction. This study aimed to address functional outcomes, complications, and morbidity associated with the fibula resection in a consecutive series of mandibular reconstruction using this technique in skeletally immature patients.

Methods: Functional outcomes in terms of maximal mouth opening capacity, patient-reported eating ability, occlusion, and gait were retrospectively reviewed in 34 consecutive pediatric patients (18 males, 16 females) who underwent mandibular reconstruction using the vascularized free fibula flap.

Notch4 signaling limits regulatory T-cell-mediated tissue repair and promotes severe lung inflammation in viral infections.

A cardinal feature of COVID-19 is lung inflammation and respiratory failure. In a prospective multi-country cohort of COVID-19 patients, we found that increased Notch4 expression on circulating regulatory T (Treg) cells was associated with disease severity, predicted mortality, and declined upon recovery. Deletion of Notch4 in Treg cells or therapy with anti-Notch4 antibodies in conventional and humanized mice normalized the dysregulated innate immunity and rescued disease morbidity and mortality induced by a synthetic analog of viral RNA or by influenza H1N1 virus.

Type III interferons disrupt the lung epithelial barrier upon viral recognition.

Viral infections of the lower respiratory tract are a leading cause of mortality. Mounting evidence indicates that most severe cases are characterized by aberrant immune responses and do not depend on viral burden. In this study, we assessed how type III interferons (IFN-λ) contribute to the pathogenesis induced by RNA viruses.

Type III interferons: Balancing tissue tolerance and resistance to pathogen invasion.

Type III IFNs, or IFN-λ, are the newest members of the IFN family and were long believed to play roles that were redundant with those of type I IFNs. However, IFN-λ displays unique traits that delineate them as primary protectors of barrier integrity at mucosal sites. This unique role stems both from the restricted expression of IFN-λ receptor, confined to epithelial cells and to a limited pool of immune cells, and from unique immunomodulatory properties of IFN-λ.

Intersection of phosphate transport, oxidative stress and TOR signalling in Candida albicans virulence.

Phosphate is an essential macronutrient required for cell growth and division. Pho84 is the major high-affinity cell-surface phosphate importer of Saccharomyces cerevisiae and a crucial element in the phosphate homeostatic system of this model yeast. We found that loss of Candida albicans Pho84 attenuated virulence in Drosophila and murine oropharyngeal and disseminated models of invasive infection, and conferred hypersensitivity to neutrophil killing.

Interferon (IFN)-λ Takes the Helm: Immunomodulatory Roles of Type III IFNs.

Type III interferons (IFNs) (or IFN-λ) are the latest addition to the IFN family. Even though they share little protein homology with type I IFN, both exhibit remarkable functional similarities: each can be induced in response to viral infections, and both lead to Janus kinases (JAK) and signal transducer and activator of transcription (STAT) activation. The JAK/STAT pathway induces antiviral responses and IFN-stimulated gene transcription.

Effect of an enzymatic treatment with cellulase and mannanase on the structural properties of Nannochloropsis microalgae.

The effects of an enzymatic treatment with cellulase and mannanase on the properties of marine microalgae Nannochloropsis sp. were investigated. The combined use of these enzymes synergistically promoted the recovery of lipids from the microalgae, increasing the extraction yield from 40.

Skin infections are eliminated by cooperation of the fibrinolytic and innate immune systems.

Nuclear factor of activated T cells (NFAT) is activated in innate immune cells downstream of pattern recognition receptors, but little is known about NFAT's functions in innate immunity compared with adaptive immunity. We show that early activation of NFAT balances the two major phases of the innate response to skin infections: the protective containment (abscess) and the elimination (expulsion) phases. During the early containment phase, transforming growth factor- (TGF-) induces the deposit of collagen around newly recruited polymorphonuclear cells to prevent microbial spreading.

IFN-λ suppresses intestinal inflammation by non-translational regulation of neutrophil function.

Interferon-λ (IFN-λ) is a central regulator of mucosal immunity; however, its signaling specificity relative to that of type I interferons is poorly defined. IFN-λ can induce antiviral interferon-stimulated genes (ISGs) in epithelia, while the effect of IFN-λ in non-epithelial cells remains unclear. Here we report that neutrophils responded to IFN-λ.

Preparation of Single-cell Suspensions for Cytofluorimetric Analysis from Different Mouse Skin Regions.

The skin is a barrier organ that interacts with the external environment. Being continuously exposed to potential microbial invasion, the dermis and epidermis home a variety of immune cells in both homeostatic and inflammatory conditions. Tools to obtain skin cell release for cytofluorimetric analyses are, therefore, very useful in order to study the complex network of immune cells residing in the skin and their response to microbial stimuli.

An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells.

Dendritic cells (DCs) use pattern recognition receptors to detect microorganisms and activate protective immunity. These cells and receptors are thought to operate in an all-or-nothing manner, existing in an immunologically active or inactive state. Here, we report that encounters with microbial products and self-encoded oxidized phospholipids (oxPAPC) induce an enhanced DC activation state, which we call "hyperactive.

An Evaluation of the Pedestrian Classification in a Multi-Domain Multi-Modality Setup.

The objective of this article is to study the problem of pedestrian classification across different light spectrum domains (visible and far-infrared (FIR)) and modalities (intensity, depth and motion). In recent years, there has been a number of approaches for classifying and detecting pedestrians in both FIR and visible images, but the methods are difficult to compare, because either the datasets are not publicly available or they do not offer a comparison between the two domains. Our two primary contributions are the following: (1) we propose a public dataset, named RIFIR , containing both FIR and visible images collected in an urban environment from a moving vehicle during daytime; and (2) we compare the state-of-the-art features in a multi-modality setup: intensity, depth and flow, in far-infrared over visible domains.

Pedestrian detection in far-infrared daytime images using a hierarchical codebook of SURF.

One of the main challenges in intelligent vehicles concerns pedestrian detection for driving assistance. Recent experiments have showed that state-of-the-art descriptors provide better performances on the far-infrared (FIR) spectrum than on the visible one, even in daytime conditions, for pedestrian classification. In this paper, we propose a pedestrian detector with on-board FIR camera.

Microbe- and danger-induced inflammation.

The ability of the immune system to give rise to an effective response against pathogens while maintaining tolerance towards self-tissues has always been an object of keen interest for immunologist. Over the years, different theories have been proposed to explain if and how the immune system is able to discriminate between self and non-self, including the Infectious Non-self theory from Charles Janeway and Polly Matzinger's Danger theory. Nowadays we know Janeway's theory is largely true, however the immune system does respond to injured, stressed and necrotic cells releasing danger signals (DAMPs) with a potent inflammatory response.

Small Molecular Aryl Acetylenes: Chemically Tailoring High-Efficiency Organic Semiconductors for Solar Cells and Field-Effect Transistors.

Over the last two decades, ever increasing interest has been focused on π-conjugated triple-bond-containing systems, namely, (poly)aryl acetylenes, as a very promising class of semiconducting materials, owing to the availability of flexible/efficient synthetic protocols and the new conception of their conformational and steric advantages. In this review, the major design/synthetic strategies used to obtain molecular aryl acetylene semiconductors are discussed. A brief discussion of their key properties as well as their performance in organic field-effect transistors and photovoltaic cell applications is also included.

IL-15 cis presentation is required for optimal NK cell activation in lipopolysaccharide-mediated inflammatory conditions.

Natural killer (NK) cells have antitumor, antiviral, and antibacterial functions, and efforts are being made to manipulate them in immunotherapeutic approaches. However, their activation mechanisms remain poorly defined, particularly during bacterial infections. Here, we show that upon lipopolysaccharide or E.

Systemically administered DNA and fowlpox recombinants expressing four vaccinia virus genes although immunogenic do not protect mice against the highly pathogenic IHD-J vaccinia strain.

The first-generation smallpox vaccine was based on live vaccinia virus (VV) and it successfully eradicated the disease worldwide. Therefore, it was not administered any more after 1980, as smallpox no longer existed as a natural infection. However, emerging threats by terrorist organisations has prompted new programmes for second-generation vaccine development based on attenuated VV strains, which have been shown to cause rare but serious adverse events in immunocompromised patients.