Autoinflammatory diseases are conditions in which pathogenic inflammation arises primarily through antigen-independent hyperactivation of immune pathways. First recognized just over 2 decades ago, ...the autoinflammatory disease spectrum has expanded rapidly to include more than 40 distinct monogenic conditions. Related mechanisms contribute to common conditions such as gout and cardiovascular disease. Here, we review the basic concepts underlying the "autoinflammatory revolution" in the understanding of immune-mediated disease and introduce major categories of monogenic autoinflammatory disorders recognized to date, including inflammasomopathies and other IL-1-related conditions, interferonopathies, and disorders of nuclear factor kappa B and/or aberrant TNF activity. We highlight phenotypic presentation as a reflection of pathogenesis and outline a practical approach to the evaluation of patients with suspected autoinflammation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The dual‐ion battery (DIB) is a promising energy storage system that demonstrates high‐power characteristics and fast‐charging capability. However, conventional electrolytes are not compatible with ...the high‐voltage graphite cathode and the reactive Li metal anode, thus leading to the poor cycle stability and low Coulombic efficiency of the DIB. Here, an all‐fluorinated electrolyte is reported that can enable a highly stable operation of the graphite||Li DIB up to 5.2 V by forming robust and less‐resistive passivation films on both electrodes to reduce side reactions. The electrolyte allows reversible PF6– anion insertion/extraction and Li+ cation plating/stripping in the graphite||Li battery, achieving stable cycling with 94.5% capacity retention over 5000 cycles at 500 mA g–1, high capacity utilization of 91.8% of the available charge capacity at 50 C (5000 mA g–1), and also minimal self‐discharge. At a low temperature of 0 °C, this all‐fluorinated electrolyte exhibits 97.8% of the room temperature reversible capacity, along with ≈100% capacity retention after more than 3000 cycles, at 5 C. This work sheds a new light on the development of fluorinated electrolytes for high voltage and long‐lasting DIBs.
An all‐fluorinated electrolyte enables reversible PF6– insertion/extraction in a high‐voltage cathode (5.2 V) and Li+ plating/stripping on a reactive Li metal anode. The graphite||Li battery demonstrates stable cycling with 94.5% capacity retention over 5000 cycles, no capacity fading upon 3000 cycles at 0 °C, ultrafast charging capability up to 50 C (5000 mA g–1) with 91.8% capacity utilization and a low self‐discharge rate.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Deficiency of adenosine deaminase 2 (DADA2) is a monogenic form of systemic vasculopathy that often presents during early childhood. Linked to biallelic mutations in
(previously
), DADA2 was ...initially described as a syndrome of recurrent fever, livedo racemosa, early-onset strokes, and peripheral vasculopathy that resembles polyarteritis nodosum. However, the wide spectrum of clinical findings and heterogeneity of disease, even among family members with identical mutations, is increasingly recognized. Evidence of systemic inflammation and vasculopathy is not uniformly present in DADA2 patients and some can remain asymptomatic through adulthood. Humoral immunodeficiency characterized by low immunoglobulin levels and increased risk of infection is another common feature of DADA2. Variable cytopenias including pure red cell aplasia that mimics Diamond-Blackfan anemia can also be primary manifestations of DADA2. How defects in a single gene translate into these heterogeneous presentations remains to be answered. In this review, we will summarize lessons learned from the pleiotropic clinical manifestations of DADA2.
Poor outcomes in COVID‐19 correlate with clinical and laboratory features of cytokine storm syndrome. Broad screening for cytokine storm and early, targeted antiinflammatory therapy may prevent ...immunopathology and could help conserve limited health care resources. While studies are ongoing, extrapolating from clinical experience in cytokine storm syndromes may benefit the multidisciplinary teams caring for patients with severe COVID‐19.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Ly6 family proteins in neutrophil biology Lee, Pui Y.; Wang, Jun‐Xia; Parisini, Emilio ...
Journal of leukocyte biology,
10/2013, Volume:
94, Issue:
4
Journal Article
Peer reviewed
Review of the structure, expression, and function of members of the Ly6 gene family, with a focus on their role in neutrophil biology.
The murine Ly6 complex was identified 35 years ago using ...antisera to lymphocytes. With advances in mAb development, molecular cloning, and genome sequencing, >20 structurally related genes have been identified within this complex on chromosome 15. All members of the Ly6 family and their human homologues share the highly conserved LU domain and most also possess a GPI anchor. Interestingly, many Ly6 proteins are expressed in a lineage‐specific fashion, and their expression often correlates with stages of differentiation. As a result, Ly6 proteins are frequently used as surface markers for leukocyte subset identification and targets for antibody‐mediated depletion. Murine neutrophils display prominent surface expression of several Ly6 proteins, including Ly6B, Ly6C, and Ly6G. Although the physiology of most Ly6 proteins is not well understood, a role in neutrophil functions, such as migration, is recognized increasingly. In this review, we will provide an overview of the Ly6 complex and discuss, in detail, the specific Ly6 proteins implicated in neutrophil biology.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
New anticancer platinum(II) compounds with distinctive modes of action are appealing alternatives to combat the drug resistance and improve the efficacy of clinically used platinum chemotherapy. ...Herein, we describe a rare example of an antitumor PtII complex targeting a tumor‐associated protein, rather than DNA, under cellular conditions. Complex (bis‐NHC)Pt(bt)PF6 (1 a; Hbt=1‐(3‐hydroxybenzobthiophen‐2‐yl)ethanone) overcomes cisplatin resistance in cancer cells and displays significant tumor growth inhibition in mice with higher tolerable doses compared to cisplatin. The cellular Pt species shows little association with DNA, and localizes in the cytoplasm as revealed by nanoscale secondary ion mass spectrometry. An unbiased thermal proteome profiling experiment identified asparagine synthetase (ASNS) as a molecular target of 1 a. Accordingly, 1 a treatment reduced the cellular asparagine levels and inhibited cancer cell proliferation, which could be reversed by asparagine supplementation. A bis‐NHC‐ligated Pt species generated from the hydrolysis of 1 a forms adducts with thiols and appears to target an active‐site cysteine of ASNS.
The platinum complex (bis‐NHC)Pt(bt)PF6 (1 a) exhibits anticancer activity towards a wide range of cancer cells and displays significant in vivo tumor growth inhibition in mice. Asparagine synthetase (ASNS) was identified as a molecular target of 1 a. Binding studies suggest that (bis‐NHC)Pt2+ forms adducts with thiols and targets the active‐site N‐terminal cysteine of ASNS.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
BACKGROUNDPediatric SARS-CoV-2 infection can be complicated by a dangerous hyperinflammatory condition termed multisystem inflammatory syndrome in children (MIS-C). The clinical and immunologic ...spectrum of MIS-C and its relationship to other inflammatory conditions of childhood have not been studied in detail.METHODSWe retrospectively studied confirmed cases of MIS-C at our institution from March to June 2020. The clinical characteristics, laboratory studies, and treatment response were collected. Data were compared with historic cohorts of Kawasaki disease (KD) and macrophage activation syndrome (MAS).RESULTSTwenty-eight patients fulfilled the case definition of MIS-C. Median age at presentation was 9 years (range: 1 month to 17 years); 50% of patients had preexisting conditions. All patients had laboratory confirmation of SARS-CoV-2 infection. Seventeen patients (61%) required intensive care, including 7 patients (25%) who required inotrope support. Seven patients (25%) met criteria for complete or incomplete KD, and coronary abnormalities were found in 6 cases. Lymphopenia, thrombocytopenia, and elevation in inflammatory markers, D-dimer, B-type natriuretic peptide, IL-6, and IL-10 levels were common but not ubiquitous. Cytopenias distinguished MIS-C from KD and the degree of hyperferritinemia and pattern of cytokine production differed between MIS-C and MAS. Immunomodulatory therapy given to patients with MIS-C included intravenous immune globulin (IVIG) (71%), corticosteroids (61%), and anakinra (18%). Clinical and laboratory improvement were observed in all cases, including 6 cases that did not require immunomodulatory therapy. No mortality was recorded in this cohort.CONCLUSIONMIS-C encompasses a broad phenotypic spectrum with clinical and laboratory features distinct from KD and MAS.FUNDINGThis work was supported by the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Institute of Allergy and Infectious Diseases; Rheumatology Research Foundation Investigator Awards and Medical Education Award; Boston Children's Hospital Faculty Career Development Awards; the McCance Family Foundation; and the Samara Jan Turkel Center.
Metal N‐heterocyclic carbene (NHC) complexes are a promising class of anti‐cancer agents displaying potent in vitro and in vivo activities. Taking a multi‐faceted approach employing two clickable ...photoaffinity probes, herein we report the identification of multiple molecular targets for anti‐cancer active pincer gold(III) NHC complexes. These complexes display potent and selective cytotoxicity against cultured cancer cells and in vivo anti‐tumor activities in mice bearing xenografts of human cervical and lung cancers. Our experiments revealed the specific engagement of the gold(III) complexes with multiple cellular targets, including HSP60, vimentin, nucleophosmin, and YB‐1, accompanied by expected downstream mechanisms of action. Additionally, PtII and PdII analogues can also bind the cellular proteins targeted by the gold(III) complexes, uncovering a distinct pincer cyclometalated metal–NHC scaffold in the design of anti‐cancer metal medicines with multiple molecular targets.
On target: Anti‐cancer active pincer cyclometalated gold(III) complexes containing N‐heterocyclic carbene ligands have been identified to be a type of multi‐target anti‐cancer agent by using a combined photoaffinity labelling and click chemistry approach. The PdII and PtII analogues can competitively bind to the same cellular targets.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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