Inflammasomes are critical sentinels of the innate immune system that respond to threats to the host through recognition of distinct molecules, known as pathogen- or damage-associated molecular ...patterns (PAMPs/DAMPs), or disruptions of cellular homeostasis, referred to as homeostasis-altering molecular processes (HAMPs) or effector-triggered immunity (ETI). Several distinct proteins nucleate inflammasomes, including NLRP1, CARD8, NLRP3, NLRP6, NLRC4/NAIP, AIM2, pyrin, and caspases-4/-5/-11. This diverse array of sensors strengthens the inflammasome response through redundancy and plasticity. Here, we present an overview of these pathways, outlining the mechanisms of inflammasome formation, subcellular regulation, and pyroptosis, and discuss the wide-reaching effects of inflammasomes in human disease.
Inflammasomes are critical initiators of inflammation and adaptive immunity with far-reaching effects on human health and disease. This review provides a 360° view of the mechanisms of inflammasome formation, subcellular regulation, and their effects on cell death and disease.
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•Carbon dots were synthesized by microplasma in 20 min.•Isopropanol was used as the only reactant.•Functional groups (CO, OH) were attached to carbon dots during plasma ...reaction.•Synthesized carbon dots own a tunable excitation-dependent emission property.
Carbon dots have recently emerged and gained much interest as a new class of carbon nanomaterials especially suited for biological applications owing to their characteristic advantages such as non-toxicity, bio-compatibility, and element abundance. In this study, a fast and effective method was developed for the synthesis of fluorescent carbon dots by microplasma technology, at atmospheric pressure, using isopropanol as the only reactant. Characterizations of the synthesized carbon dots including the investigation of their structure, morphology and optical properties were performed. The results show that the carbon dots produced have a narrow size distribution (average diameter of 1.78 nm) and are amorphous and graphitic in nature. The photoluminescent study indicates that the carbon dots present an excitation-dependent emission property with the excitation wavelengths in a range of 310–410 nm. The high density electrons produced by microplasma induce the chemical reactions and accelerate the formation process of functional groups doped carbon dots.
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•N-doped CDs with an average size of 5.98 nm were synthesized by microplasma.•The synthesized N-CDs showed intense blue emission under a UV lamp.•The quantum yield was up to 9.9% at ...excitation wavelength of 390 nm.•Effect of plasma parameters on surface group and PL property of N-CDs was explored.•Electrode size has an effect on the electron density, resulting a yield up to 0.42%.
In this study, an effective approach was presented for the synthesis of N-doped carbon dots via a microplasma-assisted process at atmospheric pressure. The effects of operation parameters on the surface groups and photoluminescence (PL) property of carbon dots were studied in detail. Nitrogen element was successfully doped as NH group and pyrrolic–like structure in the carbon dots. The morphology, structures, chemical compositions and photoluminescence properties of N-doped carbon dots were systematically characterized. The generated chemical species and mechanism were monitored and studied by optical emission spectroscopy. The synthesized particles owned excitation-dependent emission property with a quantum yield up to 9.90%. The plasma treatment time and operating voltage affect the carbonization degree, doping state of nitrogen and particle size, resulting in different PL behaviours. The variation of electrode sizes has slight effects on the yield of N-doped carbon dots from 0.31% to 0.42% owing to the differences in electron density.
Liver malignancies are among the tumor types that are resistant to immune checkpoint inhibition therapy. Tumor‐associated macrophages (TAMs) are highly enriched and play a major role in inducing ...immunosuppression in liver malignancies. Herein, CCL2 and CCL5 are screened as two major chemokines responsible for attracting TAM infiltration and inducing their polarization toward cancer‐promoting M2‐phenotype. To reverse this immunosuppressive process, an innovative single‐domain antibody that bispecifically binds and neutralizes CCL2 and CCL5 (BisCCL2/5i) with high potency and specificity is directly evolved. mRNA encoding BisCCL2/5i is encapsulated in a clinically approved lipid nanoparticle platform, resulting in a liver‐homing biomaterial that allows transient yet efficient expression of BisCCL2/5i in the diseased organ in a multiple dosage manner. This BisCCL2/5i mRNA nanoplatform significantly induces the polarization of TAMs toward the antitumoral M1 phenotype and reduces immunosuppression in the tumor microenvironment. The combination of BisCCL2/5i with PD‐1 ligand inhibitor (PD‐Li) achieves long‐term survival in mouse models of primary liver cancer and liver metastasis of colorectal and pancreatic cancers. The work provides an effective bispecific targeting strategy that could broaden the PD‐Li therapy to multiple types of malignancies in the human liver.
An innovative single‐domain antibody that bispecifically binds and neutralizes CCL2 and CCL5 (BisCCL2/5i) is evolved using yeast surface display. mRNAs encoding BisCCL2/5i or a PD‐1 ligand inhibitor (PD‐Li) are encapsulated and delivered via clinically amenable lipid nanoparticles. Combination of BisCCL2/5i with PD‐Li achieves long‐term survival in mouse models of primary liver cancer and liver metastasis of colorectal and pancreatic cancers.
Innate immunity to nucleic acids forms the backbone for anti-viral immunity and several inflammatory diseases. Upon sensing cytosolic viral RNA, retinoic acid-inducible gene-I-like receptors (RLRs) ...interact with the mitochondrial antiviral signaling protein (MAVS) and activate TANK-binding kinase 1 (TBK1) to induce type I interferon (IFN-I). TRAF3-interacting protein 3 (TRAF3IP3, T3JAM) is essential for T and B cell development. It is also well-expressed by myeloid cells, where its role is unknown. Here we report that TRAF3IP3 suppresses cytosolic poly(I:C), 5'ppp-dsRNA, and vesicular stomatitis virus (VSV) triggers IFN-I expression in overexpression systems and Traf3ip3
primary myeloid cells. The mechanism of action is through the interaction of TRAF3IP3 with endogenous TRAF3 and TBK1. This leads to the degradative K48 ubiquitination of TBK1 via its K372 residue in a DTX4-dependent fashion. Mice with myeloid-specific gene deletion of Traf3ip3 have increased RNA virus-triggered IFN-I production and reduced susceptibility to virus. These results identify a function of TRAF3IP3 in the regulation of the host response to cytosolic viral RNA in myeloid cells.
Nitrogen is an essential element to plants, animals, human beings and all the other living things on earth. Nitrogen fixation, which converts inert atmospheric nitrogen into ammonia or other valuable ...substances, is a very important part of the nitrogen cycle. The Haber-Bosch process plays the dominant role in the chemical nitrogen fixation as it produces a large amount of ammonia to meet the demand from the agriculture and chemical industries. However, due to the high energy consumption and related environmental concerns, increasing attention is being given to alternative (greener) nitrogen fixation processes. Among different approaches, plasma-assisted nitrogen fixation is one of the most promising methods since it has many advantages over others. These include operating at mild operation conditions, a green environmental profile and suitability for decentralized production. This review covers the research progress in the field of plasma-assisted nitrogen fixation achieved in the past five years. Both the production of NOx and the synthesis of ammonia are included, and discussion on plasma reactors, operation parameters and plasma-catalysts are given. In addition, outlooks and suggestions for future research are also given.
Silicosis is an important industrial health problem for those workers exposed to silica. The present study aimed to investigate the sensitivity and specificity of combined detection of biomarkers in ...early auxiliary diagnosis of silicosis, the risk factors of silicosis were also studied. The study sample comprised 65 workers who had clinical silicosis and 70 matched control subjects who were exposed to silica but did not have clinical silicosis. The levels of superoxide dismutase, malondialdehyde, interleukin 6 (IL-6), tumor necrosis factor-alpha, and cholinesterases in the serum of 135 subjects were measured. After completing the biochemical assays, a logistic regression model based on the above biochemical determination results was established, and the receiver operating characteristic curve was used for judging the discrimination ability of different statistical indexes. The expression levels of MDA, IL-6, and TNF-alpha in serum samples of patients with stage I silicosis and MDA and IL-6 in serum samples of patients with stage II silicosis were all significantly higher. Results from logistic regression analysis showed that ChEs were protective factors for silicosis, while age, chronic respiratory symptoms, IL-6, and MDA were risk factors. The areas under the ROC curve (AUC) were 0.86 (IL-6), 0.81 (MDA), and 0.65 (TNF-alpha or ChEs). AUC-ROC = 0.90 (95%CI:0.84–0.95). The diagnostic efficiency of IL-6 combined with MDA and TNF-alpha was better than that of any single biomarker.
Tumor resistance is a major hurdle to anti-Her2/neu Ab-based cancer therapy. Current strategies to overcome tumor resistance focus on tumor cell-intrinsic resistance. However, the extrinsic ...mechanisms, especially the tumor microenvironment, also play important roles in modulating the therapeutic response and resistance of the Ab. In this study, we demonstrate that tumor progression is highly associated with TAMs with immune-suppressive M2 phenotypes, and deletion of TAMs markedly enhanced the therapeutic effects of anti-Her2/neu Ab in a HER2/neu-dependent breast cancer cell TUBO model. Tumor local delivery of IL-21 can skew TAM polarization away from the M2 phenotype to a tumor-inhibiting M1 phenotype, which rapidly stimulates T cell responses against tumor and dramatically promotes the therapeutic effect of anti-Her2 Ab. Skewing of TAM polarization by IL-21 relies substantially on direct action of IL-21 on TAMs rather than stimulation of T and NK cells. Thus, our findings identify the abundant TAMs as a major extrinsic barrier for anti-Her2/neu Ab therapy and present a novel approach to combat this extrinsic resistance by tumor local delivery of IL-21 to skew TAM polarization. This study offers a therapeutic strategy to modulate the tumor microenvironment to overcome tumor-extrinsic resistance.
An equiatomic CuFeMnNi high-entropy alloy (HEA) was synthesized and homogenized at 1000 °C to achieve a microstructure of single face centered cubic phase based on CALPHAD (CALculation of PHAse ...Diagrams) prediction. The strength and ductility of this Co-free (low cost) HEA can be tuned through thermomechanical processing (cold rolling and annealing at temperatures ranging from 650 °C to 950 °C). Electron backscattered diffraction, transmission electron microscopy and scanning transmission electron microscopy techniques were used to characterize the deformation microstructure of this new HEA. The results show that plastic deformation was achieved through the slip of full dislocations with Burgers vector of a/2 < 110 > . No dissociated dislocations and deformation twins were observed, indicating that this alloy poses high stacking-fault energy, which is supported by first principle calculations. The research suggests that further improvement on the mechanical properties of this alloy can be achieved by reducing stacking-fault energy via alloying, providing a promising low-cost alternative to CoCrFeMnNi HEAs for engineering applications.
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