Beyond Antagonism: IL-4 Exploits TNF signaling to Shape Its Gene Expression Signature in Monocytes and Macrophages.

Investigation of crosstalk between antagonistic pro- and anti-inflammatory cytokines has focused on mechanisms and functional consequences of cross-inhibition. We investigated cross-regulation between proinflammatory TNF and anti-inflammatory IL-4 in primary human monocytes and in a skin wound-healing model. Surprisingly, TNF functioned mainly as a costimulator of IL-4-induced gene expression, whereas IL-4 selectively inhibited the TNF-induced IFN response, leaving inflammatory gene expression mostly intact.

Opposing regulation of TNF responses by IFN-γ and a PGE2-cAMP axis that is apparent in rheumatoid and immune checkpoint inhibitor-induced arthritis human IL-1β+ macrophages.

IL-1β-expressing macrophages have been described in rheumatoid arthritis (RA), immune checkpoint inhibitor-induced inflammatory arthritis (ICI-arthritis), and pancreatic cancer and proposed to be pathogenic. IL-1β+ macrophages express genes cooperatively induced by PGE2 and TNF signaling, but mechanisms that induce these cells are not known. We used an integrated transcriptomic and epigenomic analysis in primary human monocytes to study PGE2-TNF crosstalk, and how it is regulated by IFN-γ, as occurs in RA synovial macrophages.

IL-10 targets IRF transcription factors to suppress IFN and inflammatory response genes by epigenetic mechanisms.

Interleukin-10 (IL-10) is pivotal in suppressing innate immune activation, in large part by suppressing induction of inflammatory genes. Despite decades of research, the molecular mechanisms underlying this inhibition have not been resolved. Here we utilized an integrated epigenomic analysis to investigate IL-10-mediated suppression of LPS and TNF responses in primary human monocytes.

Pediatric eosinophilic granulomatosis with polyangiitis presenting as a mediastinal mass in a 6-year-old boy.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a small vessel vasculitis characterized by asthma, eosinophilia, and small vessel necrotizing granulomatosis with annual incidence of 0.5-4.2 cases per million.

Diketopyrrolopyrrole-based Donor-Acceptor Covalent Organic Frameworks for Iodine Capture.

The recovery of radioactive iodine from nuclear waste and contaminated water sources is a critical environmental concern, which poses significant technical challenges. Herein, the study has demonstrated that tuning the electronic properties of diketopyrrolopyrrole-based donor-acceptor covalent organic frameworks (COFs) enhances iodine trapping, improves charge transport, and strengthens iodine interactions - establishing a structure-property relationship. This tuning is achieved by synthesizing COFs with the diketopyrrolopyrrole-based linker 3,6-bis(4-(1,3-dioxolan-2-yl)phenyl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione (DKP) in combination with either the electron acceptor 4,4',4″-(1,3,5-triazine-2,4,6-triyl)trianiline (TTT-DKP) or the electron donor N,N-bis(4-aminophenyl)benzene-1,4-diamine (TAPA-DKP) linkers.

Mechanosensing regulates pDC activation in the skin through NRF2 activation.

Plasmacytoid DCs (pDCs) infiltrate the skin, chronically produce type I interferon (IFN-I), and promote skin lesions and fibrosis in autoimmune patients. However, what controls their activation in the skin is unknown. Here, we report that increased stiffness inhibits the production of IFN-I by pDCs.

Covalent Organic Frameworks for Photocatalysis.

The global energy crisis and environmental concerns are driving research into renewable energy and sustainable energy conversion and storage technologies. Solar energy, as an ideal sustainable resource, has significant potential to contribute to the goal of net-zero carbon emissions if effectively harnessed and converted into a reliable and storable form of energy. Photocatalysts have the potential to convert sunlight into chemical energy carriers.

Transgelin 2 guards T cell lipid metabolism and antitumour function.

Mounting effective immunity against pathogens and tumours relies on the successful metabolic programming of T cells by extracellular fatty acids. Fatty-acid-binding protein 5 (FABP5) has a key role in this process by coordinating the efficient import and trafficking of lipids that fuel mitochondrial respiration to sustain the bioenergetic requirements of protective CD8 T cells. However, the mechanisms that govern this immunometabolic axis remain unexplored.

Covalent Organic Framework Catalyzed Amide Synthesis Directly from Alcohol Under Red Light Excitation.

The dehydrogenative coupling of alcohols and amines to form amide bonds is typically catalysed by homogeneous transition metal catalysts at high temperatures ranging from 130-140 °C. In our pursuit of an efficient and recyclable photocatalyst capable of conducting this transformation at room temperature, we report herein a COF-mediated dehydrogenative synthesis. The TTT-DHTD COF was strategically designed to incorporate a high density of functional units, specifically dithiophenedione, to trap photogenerated electrons and effectively facilitate hydrogen atom abstraction reactions.

Staphyloccocus aureus biofilm, in absence of planktonic bacteria, produces factors that activate counterbalancing inflammatory and immune-suppressive genes in human monocytes.

Staphyloccocus aureus (S. aureus) is a major bacterial pathogen in orthopedic periprosthetic joint infection (PJI). S.

Interferons and epigenetic mechanisms in training, priming and tolerance of monocytes and hematopoietic progenitors.

Training and priming of innate immune cells involve preconditioning by PAMPs, DAMPs, and/or cytokines that elicits stronger induction of inflammatory genes upon secondary challenge. Previous models distinguish training and priming based upon whether immune activation returns to baseline prior to secondary challenge. Tolerance is a protective mechanism whereby potent stimuli induce refractoriness to secondary challenge.

Locus folding mechanisms determine modes of antigen receptor gene assembly.

The dynamic folding of genomes regulates numerous biological processes, including antigen receptor (AgR) gene assembly. We show that, unlike other AgR loci, homotypic chromatin interactions and bidirectional chromosome looping both contribute to structuring Tcrb for efficient long-range V(D)J recombination. Inactivation of the CTCF binding element (CBE) or promoter at the most 5'Vβ segment (Trbv1) impaired loop extrusion originating locally and extending to DβJβ CBEs at the opposite end of Tcrb.

Transgelin 2 guards T cell lipid metabolic programming and anti-tumor function.

Mounting effective immunity against pathogens and tumors relies on the successful metabolic programming of T cells by extracellular fatty acids. During this process, fatty-acid-binding protein 5 (FABP5) imports lipids that fuel mitochondrial respiration and sustain the bioenergetic requirements of protective CD8 T cells. Importantly, however, the mechanisms governing this crucial immunometabolic axis remain unexplored.

A Thiazole-linked Covalent Organic Framework for Lithium-Sulphur Batteries.

Lithium-sulphur (Li-S) batteries are a promising alternative power source, as they can provide a higher energy density than current lithium-ion batteries. Porous materials are often used as cathode materials as they can act as a host for sulphur in such batteries. Recently, covalent organic frameworks (COFs) have also been used, however they typically suffer from stability issues, resulting in limited and thus insufficient durability under practical conditions and applications.

Bcl-xL is translocated to the nucleus via CtBP2 to epigenetically promote metastasis.

Besides its mitochondria-based anti-apoptotic role, Bcl-xL also travels to the nucleus to promote cancer metastasis by upregulating global histone H3 trimethyl Lys4 (H3K4me3) and TGFβ transcription. How Bcl-xL is translocated into the nucleus and how nuclear Bcl-xL regulates H3K4me3 modification are not understood. Here, we report that C-terminal Binding Protein 2 (CtBP2) binds Bcl-xL via its N-terminus and translocates Bcl-xL into the nucleus.

Chronic activation of pDCs in autoimmunity is linked to dysregulated ER stress and metabolic responses.

Plasmacytoid dendritic cells (pDCs) chronically produce type I interferon (IFN-I) in autoimmune diseases, including systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). We report that the IRE1α-XBP1 branch of the unfolded protein response (UPR) inhibits IFN-α production by TLR7- or TLR9-activated pDCs. In SSc patients, UPR gene expression was reduced in pDCs, which inversely correlated with IFN-I-stimulated gene expression.

Ayurvedic Herbal Therapies: A Review of Treatment and Management of Dementia.

Dementia has been characterized by atypical neurological syndromes and several cognitive deficits, such as extended memory loss, strange behavior, unusual thinking, impaired judgment, impotence, and difficulty with daily living activities. Dementia is not a disease, but it is caused by several neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Lewy's bodies. Several drugs and remedies are indicated for alleviating unusual cognitive decline, but no effective pharmacological treatment regimens are available without side effects.

Dynamic link between bilateral FDI, the quality of environment and institutions: evidence from G20 countries.

The sustenance of a clean, natural, and relatively less tampered environment is one of the most important apprehensions of contemporary households, firms, and governments in the globalized world. Both developing and developed countries rely heavily on foreign direct investments (FDI) and institutional arrangements for economic prosperity and have feedback repercussions about environmental quality. Thus, the current paper attempts to explore such a triplex integrated linkage among bilateral FDI, institutional quality, and environmental quality proxied by CO emissions intensity on each other for 19 selected G20 countries during 2009-2017.

Potential Biomarkers Associated with Multiple Sclerosis Pathology.

Multiple sclerosis (MS) is a complex disease of the central nervous system (CNS) that involves an intricate and aberrant interaction of immune cells leading to inflammation, demyelination, and neurodegeneration. Due to the heterogeneity of clinical subtypes, their diagnosis becomes challenging and the best treatment cannot be easily provided to patients. Biomarkers have been used to simplify the diagnosis and prognosis of MS, as well as to evaluate the results of clinical treatments.

Role of polymorphisms in dopamine synthesis and metabolism genes and association of DBH haplotypes with Parkinson's disease among North Indians.

Objectives: Genetic and non-genetic components are believed to govern the etiology of common complex traits such as Parkinson's disease (PD). In view of the biochemical evidence of depleted dopamine levels in the affected brains and also the most common and effective therapeutic modality of administration of levodopa in PD, genes from the dopaminergic pathway emerge as major determinants. We have earlier shown the role of DRD4-120 bp duplication marker in PD susceptibility.

Do motor control genes contribute to interindividual variability in decreased movement in patients with pain?

Background: Because excessive reduction in activities after back injury may impair recovery, it is important to understand and address the factors contributing to the variability in motor responses to pain. The current dominant theory is the "fear-avoidance model", in which the some patients' heightened fears of further injury cause them to avoid movement. We propose that in addition to psychological factors, neurochemical variants in the circuits controlling movement and their modification by pain may contribute to this variability.

Reliable screening for a pain-protective haplotype in the GTP cyclohydrolase 1 gene (GCH1) through the use of 3 or fewer single nucleotide polymorphisms.

Background: A haplotype in the GTP cyclohydrolase 1 (dopa-responsive dystonia) gene (GCH1) is associated with decreased persistent pain. The aim of the present study was to develop a screening method for the pain-protective haplotype.

Methods: Complete genetic information for all 15 GCH1 DNA positions constituting the pain-protective GCH1 haplotype was available from 278 patients.