MARCH5 promotes STING pathway activation by suppressing polymer formation of oxidized STING.

Stimulator of interferon genes (STING) is a core DNA sensing adaptor in innate immune signaling. STING activity is regulated by a variety of post-translational modifications (PTMs), including phosphorylation, ubiquitination, sumoylation, palmitoylation, and oxidation, as well as the balance between active and inactive polymer formation. It remains unclear, though, how different PTMs and higher order structures cooperate to regulate STING activity.

Strong Anionic Repulsion for Fast Na Kinetics in P2-Type Layered Oxides.

An intriguing mechanism for enabling fast Na kinetics during oxygen redox (OR) is proposed to produce high-power-density cathodes for sodium-ion batteries (SIBs) based on the P2-type oxide models, Na [Mn Ni ]O (NMNO) and Na [Ti Mn Ni ]O (NTMNO) using the "potential pillar" effect. The critical structural parameter of NTMNO lowers the Na migration barrier in the desodiated state because the electrostatic repulsion of O(2p)O(2p) that occurs between transition metal layers is combined with the chemically stiff Ti (3d)O(2p) bond to locally retain the strong repulsion effect. The NTMNO interlayer distance moderately decreases upon charging with oxygen oxidation, whereas that of NMNO decreases at a much faster rate, which can be explained by the dependence of OR activity on the coordination environment.

Intrinsic Origin of Nonhysteretic Oxygen Capacity in Conventional Na-Excess Layered Oxides.

An intriguing redox chemistry via oxygen has emerged to achieve high-energy-density cathodes and has been intensively studied for practical use of anion-utilization oxides in A-ion batteries (A: Li or Na). However, in general, the oxygen redox disappears in the subsequent discharge with a large voltage hysteresis after the first charge process for A-excess layered oxides exhibiting anion redox. Unlike these hysteretic oxygen redox cathodes, the two Na-excess oxide models NaIrO and NaRuO unambiguously exhibit nonhysteretic oxygen capacities during the first cycle, with honeycomb-ordered superstructures.

The cGAS/STING/TBK1/IRF3 innate immunity pathway maintains chromosomal stability through regulation of p21 levels.

Chromosomal instability (CIN) in cancer cells has been reported to activate the cGAS-STING innate immunity pathway via micronuclei formation, thus affecting tumor immunity and tumor progression. However, adverse effects of the cGAS/STING pathway as they relate to CIN have not yet been investigated. We addressed this issue using knockdown and add-back approaches to analyze each component of the cGAS/STING/TBK1/IRF3 pathway, and we monitored the extent of CIN by measuring micronuclei formation after release from nocodazole-induced mitotic arrest.

Intracellular calcium is a rheostat for the STING signaling pathway.

Stimulator of IFN genes (STING) is essential for the DNA-sensing innate immune pathway. Recently, evidence is emerging that suggests STING also plays important roles in autoimmunity, cancer therapy, and senescence. Although a multitude of post-translational modifications that regulate the STING pathway have been discovered, the cellular events that guide STING translocation remain unclear.

Systematic editing of synthetic RIG-I ligands to produce effective antiviral and anti-tumor RNA immunotherapies.

Retinoic acid-inducible gene I (RIG-I) recognizes double-stranded viral RNAs (dsRNAs) containing two or three 5' phosphates. A few reports of 5'-PPP-independent RIG-I agonists have emerged, but little is known about the molecular principles underlying their recognition. We recently found that the bent duplex RNA from the influenza A panhandle promoter activates RIG-I even in the absence of a 5'-triphosphate moiety.

The Cooperative Role of CD326 and CD11b Dendritic Cell Subsets for a Hapten-Induced Th2 Differentiation.

Dendritic cells (DCs) play a critical role in directing immune responses. Previous studies have identified a variety of DC subsets and elucidated their context-dependent functions that parallel those of effector Th cell subsets. However, little is known about the DC subsets responsible for differentiation of Th2 cells governing allergic contact dermatitis.

Carbonyl cyanide 3-chlorophenylhydrazone (CCCP) suppresses STING-mediated DNA sensing pathway through inducing mitochondrial fission.

Besides its important role in innate immune response to DNA virus infection, the regulatory function of STING in autoimmunity and cancer is emerging. Recently, multiple mechanisms regulating the activity of the STING pathway have been revealed. Previous study showed that carbonyl cyanide 3-chlorophenylhydrazone (CCCP), the protonophore, inhibited STING-mediated IFN-β production via disrupting mitochondrial membrane potential (MMP).

Stimulator of IFN genes-mediated DNA-sensing pathway is suppressed by NLRP3 agonists and regulated by mitofusin 1 and TBC1D15, mitochondrial dynamics mediators.

The stimulator of IFN genes (STING)-mediated DNA-sensing pathway plays an important role in the innate immune response to pathogen infection, autoimmunity, and cancer; however, its regulatory mechanism has not been fully elucidated, and we do not yet know whether the STING pathway is counter-regulated by other innate immune pathways. Here, we show that the NLRP3-activating agonists, ATP and nigericin, prevent STING pathway activation in association with mitochondrial fragmentation; however, the suppression of the STING pathway and mitochondria fission were not dependent on NLRP3 or potassium efflux. Although nigericin-induced mitochondria fission was rescued by knockdown of either dynamin-related protein 1 or TBC1 domain family member 15 (TBC1D15), which are two distinct mitochondria fission regulators, only TBC1D15 restored the activity of the STING pathway, which indicates that inflammasome-activating signals curtail STING pathway activation TBC1D15.

Extra-Large Pore Mesoporous Silica Nanoparticles for Directing in Vivo M2 Macrophage Polarization by Delivering IL-4.

Over the past decade, mesoporous silica nanoparticles (MSNs) smaller than 200 nm with a high colloidal stability have been extensively studied for systemic drug delivery. Although small molecule delivery via MSNs has been successful, the encapsulation of large therapeutic biomolecules, such as proteins or DNA, is limited due to small pore size of the conventional MSNs obtained by soft-templating. Here, we report the synthesis of mesoporous silica nanoparticles with extra-large pores (XL-MSNs) and their application to in vivo cytokine delivery for macrophage polarization.

Serum prostate-specific antigen levels and type of work in tire manufacturing workers.

Objectives: This study measures serum prostate-specific antigen (PSA) levels in tire-manufacturing workers, and attempts to find occupational or non-occupational factors that related to their PSA levels.

Methods: A total of 1,958 healthy male workers (1,699 were production workers and 259 were office workers) took PSA measurement for analysis.

Results: After adjusting for age, body mass index, hypertension, regular exercise, alcohol drinking and smoking, which were significantly related to serum PSA levels or known related factors of serum PSA levels, the geometric mean PSA levels were significantly high in the office workers (p = 0.