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LAIR1, a receptor found on immune cells, is capable of binding to collagen and is involved in immune-related diseases. However, the precise contribution of LAIR1 expressed on hepatocellular carcinoma (HCC) cells to tumor microenvironment is still unclear. In our study, bioinformatics analysis and immunofluorescence were employed to study the correlation between LAIR1 levels and clinical indicators. Transwell and scratch tests were used to evaluate how LAIR1 affected the migration and invasion of HCC cells. The chemotactic capacity and alternative activation of macrophages were investigated using RT-qPCR, transwell, and immunofluorescence. To investigate the molecular mechanisms, transcriptome sequencing analysis, Western blot, nucleus/cytoplasm fractionation, ELISA, and cytokine microarray were employed. We revealed a significant correlation between the presence of LAIR1 and an unfavorable outcome in HCC. We indicated that LAIR1 promoted migration and invasion of HCC cells through the AKT-IKKß-p65 axis. Additionally, the alternative activation and infiltration of tumor-associated macrophages induced by LAIR1 were reliant on the upregulation of IL6 and CCL5 within this axis, respectively. In conclusion, blocking LAIR1 was found to be an effective approach in combating the cancerous advancement of HCC.
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Carcinoma Hepatocelular , Movimento Celular , Neoplasias Hepáticas , Proteínas Proto-Oncogênicas c-akt , Receptores Imunológicos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , Quinase I-kappa B/metabolismo , Quinase I-kappa B/genética , Fator de Transcrição RelA/metabolismo , Fator de Transcrição RelA/genética , Linhagem Celular Tumoral , Microambiente Tumoral , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais , Macrófagos/metabolismo , Macrófagos/patologia , Proliferação de Células , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/patologia , Macrófagos Associados a Tumor/imunologia , Invasividade NeoplásicaRESUMO
BACKGROUND: Interleukin-33 (IL-33), defined as "alarming", exert diverse functions through signaling via the suppression of tumorigenicity 2 (ST2). However, the physiological roles of IL-33/ST2 signaling during acetaminophen (APAP)-induced liver injury are still poorly understood by modern medicine (AILI). This research aims to explore the relationship between IL-33/ST2 and stimulator of interferon (IFN) response cGAMP interactor 1 (STING)-mediated signal transduction. METHODS: C57BL/6N mice (WT) and IL-33-deficient mice (KO) were intraperitoneally injected with APAP (250 mg/kg). Recombinant IL-33 (500 ng/mouse) and the cGAS/STING inhibitor RU.521 (200 g/kg) were combined to treat AILI. For mechanistic research in vitro, CRISPR-mediated KD technology, immunoprecipitation, mass spectrometry, and immunofluorescence were utilized. RESULTS: We discovered that IL-33 deficient mice had increased APAP-induced hepatotoxicity, DNA accumulation, and type 1 IFN production. Mechanistic analysis revealed that IL-33/ST2 enhanced the interaction between Beclin-1 and STING, disrupting STING dimerization, IRF3 phosphorylation, nuclear transport, and IFN-1 gene transcription in HepaRG and Huh7 cells. Beclin-1 interacted with the C-terminus of STING, causing Lys338 acetylation and autophagy degradation of STING. ST2 depletion increased STING signal transduction and IFN-1 promoter activity. Surprisingly, the cGAS/STING inhibitor RU.521 and recombinant IL-33 together improved AILI in vivo. CONCLUSIONS: These results shed insight on the potential of inhibiting cGAS/STING as a therapy for AILI and emphasize the crucial role of IL-33/ST2 signaling in the regulation of APAP-induced STING signaling. Video Abstract.
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Acetaminofen , Proteína 1 Semelhante a Receptor de Interleucina-1 , Animais , Camundongos , Acetaminofen/efeitos adversos , Autofagia , Proteína Beclina-1 , Imunidade Inata/genética , Interleucina-33 , Camundongos Endogâmicos C57BL , Nucleotidiltransferases/metabolismo , Transdução de SinaisRESUMO
Metallic anodes (lithium, sodium, and zinc) are attractive for rechargeable battery technologies but are plagued by an unfavorable metal-electrolyte interface that leads to nonuniform metal deposition and an unstable solid-electrolyte interphase (SEI). Here we report the use of electrochemically labile molecules to regulate the electrochemical interface and guide even lithium deposition and a stable SEI. The molecule, benzenesulfonyl fluoride, was bonded to the surface of a reduced graphene oxide aerogel. During metal deposition, this labile molecule not only generates a metal-coordinating benzenesulfonate anion that guides homogeneous metal deposition but also contributes lithium fluoride to the SEI to improve Li surface passivation. Consequently, high-efficiency lithium deposition with a low nucleation overpotential was achieved at a high current density of 6.0 mA cm-2 A Li|LiCoO2 cell had a capacity retention of 85.3% after 400 cycles, and the cell also tolerated low-temperature (-10 °C) operation without additional capacity fading. This strategy was applied to sodium and zinc anodes as well.
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Emerging evidences have shown that long noncoding RNA (lncRNA) plays an important role in the immune escape of cancer cells. Our previous study has demonstrated that lncRNA MIAT is associated with the immune infiltration of hepatocellular carcinoma (HCC). However, the underlying mechanism of MIAT regulating the PD-L1-mediated immune escape of HCC is poorly understood. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of MIAT and PD-L1 mRNA in HCC. The relationship between MIAT, miR-411-5p, STAT3 and PD-L1 was explored by dual-luciferase reporter assay, cytotoxicity assay, Western blot and RNA immunoprecipitation (RIP). In addition, the xenograft model was established to determine the effect of MIAT on PD-L1 expression in vivo. We found that MIAT and PD-L1 were significantly upregulated in HCC tissues and the expression of PD-L1 was regulated by MIAT. The knockdown of MIAT enhanced the cytotoxicity of T cells on HCC cells. MIAT negatively regulated miR-411-5p expression, upregulated STAT3 and ultimately increased PD-L1 expression from the transcription level. The inhibition of miR-411-5p reversed STAT3 and PD-L1 expression inhibited by MIAT knockdown in HCC cells. This study suggests a novel lncRNA-mediated mechanism for HCC cells to evade the immune response; MIAT/miR-411-5p/STAT3/PD-L1 may be a novel therapeutic target for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Regulação Neoplásica da Expressão Gênica , Humanos , Imunidade , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismoRESUMO
Dental pulp stem cells (DPSCs) are capable of both self-renewal and multilineage differentiation, which play a positive role in dentinogenesis. Studies have shown that tumor necrosis factor-α (TNF-α) is involved in the differentiation of DPSCs under pro-inflammatory stimuli, but the mechanism of action of TNF-α is unknown. Rip-like interacting caspase-like apoptosis-regulatory protein kinase (RICK) is a biomarker of an early inflammatory response that plays a key role in modulating cell differentiation, but the role of RICK in DPSCs is still unclear. In this study, we identified that RICK regulates TNF-α-mediated odontogenic differentiation of DPSCs via the ERK signaling pathway. The expression of the biomarkers of odontogenic differentiation dental matrix protein-1 (DMP-1), dentin sialophosphoprotein (DSPP), biomarkers of odontogenic differentiation, increased in low concentration (1-10 ng/ml) of TNF-α and decreased in high concentration (50-100 ng/ml). Odontogenic differentiation increased over time in the odontogenic differentiation medium. In the presence of 10 ng/L TNF-α, the expression of RICK increased gradually over time, along with odontogenic differentiation. Genetic silencing of RICK expression reduced the expression of odontogenic markers DMP-1 and DSPP. The ERK, but not the NF-κB signaling pathway, was activated during the odontogenic differentiation of DPSCs. ERK signaling modulators decreased when RICK expression was inhibited. PD98059, an ERK inhibitor, blocked the odontogenic differentiation of DPSCs induced by TNF-α. These results provide a further theoretical and experimental basis for the potential use of RICK in targeted therapy for dentin regeneration.
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Diferenciação Celular , Polpa Dentária/citologia , Sistema de Sinalização das MAP Quinases , NF-kappa B/metabolismo , Odontogênese , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/metabolismo , Células-Tronco/citologia , Fator de Necrose Tumoral alfa/metabolismo , Adolescente , Humanos , Fosforilação , Proteínas Quinases/metabolismo , Fatores de Tempo , Adulto JovemRESUMO
The unique flavor of Citrus fruit depends on complex combinations of soluble sugars, organic acids, and volatile compounds. The monoterpene E-geraniol is an important volatile, contributing to flavor in sweet orange (Citrus sinensis Osbeck). Moreover, antifungal activity of E-geraniol has also been observed. However, the terpene synthase (TPS) responsible for its synthesis has not been identified in sweet orange. Terpene synthase 16 (CitTPS16) was shown to catalyze synthesis of E-geraniol in vitro, and transient overexpression of CitTPS16 in fruits and leaves of Newhall sweet orange resulted in E-geraniol accumulation in vivo. Having identified the responsible enzyme, we next examined transcriptional regulation of CitTPS16 in the fruit. Among cloned members of the AP2/ERF transcription factor gene family, CitERF71 showed a similar expression pattern to CitTPS16. Moreover, CitERF71 was able to activate the CitTPS16 promoter based on results from transient dual-luciferase assays and yeast one-hybrid assays. EMSAs showed that CitERF71 directly binds to ACCCGCC and GGCGGG motifs in the CitTPS16 promoter. These results indicate an important role for CitERF71 in transcriptional regulation of CitTP16 and, therefore, in controlling production of E-geraniol in Citrus fruit.
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Alquil e Aril Transferases/genética , Citrus sinensis/genética , Frutas/metabolismo , Proteínas de Plantas/genética , Terpenos/metabolismo , Fatores de Transcrição/genética , Monoterpenos Acíclicos , Alquil e Aril Transferases/metabolismo , Citrus sinensis/metabolismo , Filogenia , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas , Análise de Sequência de DNA , Fatores de Transcrição/metabolismoRESUMO
Aroma is a vital characteristic that determines the quality and commercial value of citrus fruits, and characteristic volatiles have been analyzed in different citrus species. In sweet orange, Citrus sinensis, the sesquiterpene (+)-valencene is a key volatile compound in the fruit peel. Valencene synthesis is catalyzed by the terpene synthase CsTPS1, but the transcriptional mechanisms controlling its gene expression are unknown. Here, the AP2/ERF (APETALA2/ethylene response factor) transcription factor, CitAP2.10, is characterized as a regulator of (+)-valencene synthesis. The expression pattern of CitAP2.10 was positively correlated with (+)-valencene content and CsTPS1 expression. Dual-luciferase assays indicated that CitAP2.10 could trans-activate the CsTPS1 promoter. Ethylene enhanced expression of CitAP2.10 and this effect was abolished by the ethylene antagonist 1-methylcyclopropene. The role and function of CitAP2.10 in (+)-valencene biosynthesis were confirmed using the Arabidopsis homolog (AtWRI1), which also transiently activated the CsTPS1 promoter. Furthermore, transient over-expression of CitAP2.10 triggered (+)-valencene biosynthesis in sweet orange fruit. These results indicate that CitAP2.10 regulates (+)-valencene synthesis via induction of CsTPS1 mRNA accumulation.
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Alquil e Aril Transferases/metabolismo , Citrus sinensis/enzimologia , Sesquiterpenos/metabolismo , Fatores de Transcrição/fisiologia , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/fisiologia , Citrus sinensis/metabolismo , Ativação Enzimática , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Regiões Promotoras Genéticas , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Transcrição/metabolismoRESUMO
The AP2/ERF gene family encodes plant-specific transcription factors. In model plants, AP2/ERF genes have been shown to be expressed in response to developmental and environmental stimuli, and many function downstream of the ethylene, biotic, and abiotic stress signaling pathways. In citrus, ethylene is effective in regulation citrus fruit quality, such as degreening and aroma. However, information about the citrus AP2/ERF family is limited, and would enhance our understanding of fruit responses to environmental stress, fruit development and quality. CitAP2/ERF genes were isolated using the citrus genome database, and their expression patterns analyzed by real-time PCR using various orange organs and samples from a fruit developmental series. 126 sequences with homologies to AP2/ERF proteins were identified from the citrus genome, and, on the basis of their structure and sequence, assigned to the ERF family (102), AP2 family (18), RAV family (4) and Soloist (2). MEME motif analysis predicted the defining AP2/ERF domain and EAR repressor domains. Analysis of transcript accumulation in Citrus sinensis cv. 'Newhall' indicated that CitAP2/ERF genes show organ-specific and temporal expression, and provided a framework for understanding the transcriptional regulatory roles of AP2/ERF gene family members in citrus. Hierarchical cluster analysis and t tests identified regulators that potentially function during orange fruit growth and development.
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Citrus/genética , Proteínas de Ligação a DNA/genética , Frutas/genética , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Proteínas de Plantas/genética , Fator de Transcrição AP-2/genética , Motivos de Aminoácidos , Arabidopsis/genética , Arabidopsis/metabolismo , Citrus/metabolismo , Proteínas de Ligação a DNA/classificação , Proteínas de Ligação a DNA/metabolismo , Frutas/metabolismo , Dados de Sequência Molecular , Especificidade de Órgãos , Oryza/genética , Oryza/metabolismo , Filogenia , Proteínas de Plantas/classificação , Proteínas de Plantas/metabolismo , Homologia de Sequência de Aminoácidos , Transdução de Sinais , Especificidade da Espécie , Fator de Transcrição AP-2/classificação , Fator de Transcrição AP-2/metabolismo , Transcrição GênicaRESUMO
Heterojunctions photocatalysts play a crucial role in achieving high solar-hydrogen conversion efficiency. In this work, we mainly focus on the charge transfer dynamics and pathways for sulfides-based Schottky junctions in the photocatalytic water splitting process to clarify the mechanism of heterostructures photocatalysis. Sulfides-based Schottky junctions (CdS/CoP and CdS/1T-MoS2) were successfully constructed for photocatalytic water splitting. Because of the higher work function of CdS than that of CoP and 1T-MoS2, the direction of the built-in electric field is from CoP or 1T-MoS2 to semiconductor. Therefore, CoP and 1T-MoS2 can act as electrons acceptors to accelerate the transfer of photo-generated electron on the surface of CdS, thus improving the charge utilization efficiency. Meanwhile, CoP and 1T-MoS2 as active sites can also promote the water dissociation and lower the H+ reduction overpotential, thus contributing to the excellent photocatalytic hydrogen production activity (23.59 mmol·h-1·g-1 and 1195.8 mol·h-1·g-1 for CdS/CoP and CdS/1T-MoS2).
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Photocatalysis represents a sustainable strategy for addressing energy shortages and global warming. The main challenges in the photocatalytic process include limited light absorption, rapid recombination of photo-induced carriers, and poor surface catalytic activity for reactant molecules. Defect engineering in photocatalysts has been proven to be an efficient approach for improving solar-to-chemical energy conversion. Sulfur vacancies can adjust the electron structure, act as electron reservoirs, and provide abundant adsorption and activate sites, leading to enhanced photocatalytic activity. In this work, we aim to elucidate the role of sulfur vacancies in photocatalytic reactions and provide valuable insights for engineering high-efficiency photocatalysts with abundant sulfur vacancies in the future. First, we delve into the fundamental understanding of photocatalysis. Subsequently, various strategies for fabricating sulfur vacancies in photocatalysts are summarized, along with the corresponding characterization techniques. More importantly, the enhanced photocatalytic mechanism, focusing on three key factors, including electron structure, charge transfer, and the surface catalytic reaction, is discussed in detail. Finally, the future opportunities and challenges in sulfur vacancy engineering for photocatalysis are identified.
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Ternary copper-antimony sulfide nanocrystals (CAS NCs) have attracted increasing attention in photovoltaics and photoelectric nanodevices due to their tunable band gaps in the near-IR regime. Although much progress in the synthesis of CAS NCs has been achieved, the selective synthesis of CAS NCs with controllable morphologies and compositions is preliminary: in particular, a facile method is still in demand. In this work, we have successfully selectively synthesized high-quality CAS NCs with diverse morphologies, compositions, and band gaps, including rectangular CuSbS2 nanosheets (NSs), trigonal-pyramidal Cu12Sb4S13 NCs, and rhombic Cu3SbS3 NSs, by cothermodecomposition of copper diethyldithiocarbamate trihydrate (Cu(Ddtc)2) and antimony diethyldithiocarbamate trihydrate (Sb(Ddtc)3). The direct and indirect band gaps of the obtained CAS NCs were systematically studied by performing Kubelka-Munk transformations of their solid-state diffuse reflectance spectra.
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Antimônio/química , Cobre/química , Nanopartículas/química , Sulfetos/química , Nanopartículas/ultraestruturaRESUMO
Due to the advanced network technology, there is almost no barrier to information dissemination, which has led to the breeding of rumors. Intended to clarify the dynamic mechanism of rumor propagation, we formulate a SIR model with time delay, forced silence function and forgetting mechanism in both homogeneous and heterogeneous networks. In the homogeneous network model, we first prove the nonnegativity of the solutions. Based on the next-generation matrix, we calculate the basic reproduction number R0. Besides, we discuss the existence of equilibrium points. Next, by linearizing the system and constructing a Lyapunov function, the local and global asymptotically stability of the equilibrium points are found. In the heterogeneous network model, we derive the basic reproduction number R00 through the analysis of a rumor-prevailing equilibrium point E∗. Moreover, we conduct the local and global asymptotic stability analysis for the equilibrium points according to the LaSalle's Invariance Principle and stability theorem. As long as the maximum spread rate ß is large enough, the rumor-prevailing point E∗ is locally asymptotically stable when R00>1. Additionally, it hits that the system exists bifurcation behavior at R00=1 due to the newly added forced silence function. Later, after adding two controllers to the system, we research the problem of optimal control. Finally, aimed at authenticating the above theoretical results, a serious of numerical simulation experiments are carried out.
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The lateral size of graphene nanosheets plays a critical role in the properties and microstructure of 3D graphene as well as their application as supports of electrocatalysts for CO2 reduction reactions (CRRs). Here, graphene oxide (GO) nanosheets with different lateral sizes (1.5, 5, and 14 µm) were utilized as building blocks for 3D graphene aerogel (GA) to research the size effects of GO on the CRR performances of 3D Au/GA catalysts. It was found that GO-L (14 µm) led to the formation of GA with large pores and a low surface area and that GO-S (1.5 µm) induced the formation of GA with a thicker wall and isolated pores, which were not conducive to the mass transfer of CO2 or its interaction with catalysts. Au/GA constructed with a suitable-sized GO (5 µm) exhibited a hierarchical porous network and the highest surface area and conductivity. As a result, Au/GA-M exhibited the highest Faradaic efficiency (FE) of CO (FECO = 81%) and CO/H2 ratio at -0.82 V (vs. a Reversible Hydrogen Electrode (RHE)). This study indicates that for 3D GA-supported catalysts, there is a balance between the improvement of conductivity, the adsorption capacity of CO2, and the inhibition of the hydrogen evolution reaction (HER) during the CRR, which is related to the lateral size of GO.
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A feasible approach to enhance the antimicrobial efficacy of ε-polylysine (PL) in applications is to form delivery complexes with delicate structures and good dispersion properties. This work aims to study the multiscale structures, properties and interactions, and edible coating applications of the electrostatic complex formed by PL and soy protein isolate (SPI). When the mass ratio of SPI to PL (SE) was between 5 and 15, especially 11, microscale solid-liquid phase separation occurred in the system due to the small absolute zeta potential. When the SE was in the range of 15-20, the system formed a stable nanoscale suspension, the average particle size and zeta potential were 191 nm and -20 mV, respectively. The physicochemical properties of the complexes were investigated including the colloidal properties, spectroscopy and interactions analysis, viscosity, contact angle, and antimicrobial activities against Escherichia coli, Staphylococcus aureus, and Penicillium expansum. Finally, the in vivo application on citrus demonstrated that the nanoscale PL/SPI electrostatic complex (SE = 20) as functional coatings has both barrier and antimicrobial activities. The study provides a novel application strategy for PL and nanoscale electrostatic complexes as postharvest coatings.
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Anti-Infecciosos , Citrus , Filmes Comestíveis , Polilisina/farmacologia , Polilisina/química , Proteínas de Soja , Eletricidade Estática , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Escherichia coliRESUMO
Impaired function of CD8+ T cells in hepatocellular carcinoma (HCC) is an important reason for acquired resistance. Compared with single-target inhibitors, small-molecule compounds that could both inhibit tumor cells and alleviate T cell exhaustion are more promising to reduce resistance. In this study, we screened immunosuppressive targets in HCC by combining cancer-immunity cycle score with weighted gene co-expression network and system analysis. Through in vitro and in vivo validation experiments, we found that one of the screened molecules, recombination signal binding protein for immunoglobulin kappa J region (RBPJ), was negatively correlated with CD8+ T cell mediated killing function. More importantly, its transcription complex inhibitor RIN1 not only inhibited the malignant biological behaviors of HCC cells by inhibiting mTOR pathway, but also reduced the expression of PD-L1 and L-kynurenine synthesis in HCC cells, thus alleviating T cell exhaustion. Meanwhile, the combination of RIN1 and anti-PD-1/PD-L1 antibodies could further activate CD8+ T cells. In short, RBPJ is an important factor regulating the function of T cells. Target inhibition of RBPJ transcription complex by small molecule compound may be a new strategy for immunotherapy of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Linfócitos T CD8-Positivos , Antígeno B7-H1/genética , Linhagem Celular , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismoRESUMO
Interleukin-33 (IL-33) functions both as a secreted cytokine and as a nuclear factor, with pleiotropic roles in cancer and immunity. Here, we explored its role in hepatocellular carcinoma (HCC) and identified that a posttranslational modification altered its nuclear activity and promoted immune escape for HCC. IL-33 abundance was overall decreased but more frequently localized to the nucleus in patient HCC tissues than in normal liver tissues. In human and mouse HCC cells in culture and in vivo, IL-33 overexpression inhibited proliferation and repressed the abundance of programmed death ligand 1 (PD-L1) at the transcriptional level by promoting the ubiquitin-dependent degradation of interferon regulatory factor 1 (IRF1). However, this interaction was disrupted by SUMOylation of IL-33 at Lys54 mediated by the E3 ligase RanBP2. IL-33 SUMOylation correlated with its nuclear localization in HCC cells and tumors. An increase in SUMOylated IL-33 in HCC cells in cocultures and in vivo stabilized IRF1 and increased PD-L1 abundance and chemokine IL-8 secretion, which prevented the activation of cytotoxic T cells and promoted the M2 polarization of macrophages, respectively. Mutating the SUMOylation site in IL-33 reversed these effects and suppressed tumor growth. These findings indicate that SUMOylation of nuclear IL-33 in HCC cells impairs antitumor immunity.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Antígeno B7-H1/metabolismo , Interleucina-33/genética , Interleucina-33/metabolismo , Fator Regulador 1 de Interferon/genética , Fator Regulador 1 de Interferon/metabolismo , Linhagem Celular TumoralRESUMO
BACKGROUND: TGF-ß is related to the function of T cells in the tumor microenvironment. However, the characteristics of TGF-ß affecting the function of CD8+ T cells in hepatocellular carcinoma (HCC) have not been clearly resolved. METHODS: In this study, flow cytometry, mass cytometry, immunohistochemistry, RNA-seq, single-cell RNA-seq, assay for transposase-accessible chromatin with high throughput sequencing, chromatin immunoprecipitation, and dual-luciferase reporter gene assay were used to study the regulatory effect and molecular mechanism of TGF-ß on HCC infiltrating CD8+ T cells. RESULTS: Here, we demonstrated that the overall effect of TGF-ß on CD8+ T cells in HCC was to activate p-p38 to induce exhaustion, but it also initiated cell-intrinsic resistance mechanisms: 1) TGF-ß upregulated the levels of p-STAT1 (S727) and promoted LAIR2 secretion; 2) the TGF-ß-p-STAT1-LAIR2 axis relieved CD8+ T cells from exhaustion, which we called "self-rescue"; 3) this "self-rescue" behavior showed time and dose limitations on TGF-ß stimulation, which was easily masked by stronger inhibitory signals; 4) the function of CD8+ T cells was improved by using TAK-981 to amplify "self-rescue" signal. CONCLUSION: Our study describes a "self-rescue" mechanism of CD8+ T cells in HCC against exhaustion and the good effects from amplifying this signal.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Linfócitos T CD8-Positivos/metabolismo , Neoplasias Hepáticas/patologia , Fator de Crescimento Transformador beta/metabolismo , Microambiente Tumoral , Fator de Transcrição STAT1RESUMO
Dual functional graphene oxide (GO) microcapsules were fabricated through self-assembly in Pickering emulsions, carrying corrosion inhibitor benzotriazole (BTA) on the microcapsule shells and encapsulating a self-healing agent epoxy monomer. The formation of the GO microcapsules was assisted by the interaction between BTA and GO, which provided robust encapsulation for the epoxy monomer. The loading capacity of BTA and epoxy monomer reached 90.5%. The addition of the GO microcapsules simultaneously promoted the corrosion protection and self-healing properties of the waterborne epoxy composite coatings. The healing efficiency of the composite coatings reached over 99.7% when the content of the microcapsules was 10 wt%. Meanwhile, the corrosion current density of the intact coatings was decreased for around 50 times.
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A new strategy for precisely controlling the growth of heterostructured nanocrystals through a dissolution-attachment process of core-shell nanocrystals is proposed. The secondary growth process of Cu-Au bimetallic nanocrystals (BNCs) comprising of a core-shell structure has been systematically investigated, which generates a variety of heterostructured Cu-Au-based nanocrystals. Various factors such as the addition of dodecanethiol and the size of the Cu-Au nanoseeds that contribute to the diverse growth of core-shell Cu-Au BNCs have been examined. A dissolution-attachment growth process is suggested on the basis of UV-vis and transmission electron microscopy measurements. In addition to the size, the shape and composition of the final nanocrystals could be controlled by this process. This new strategy will allow us to control the growth process of heterostructured nanocrystals independently from the nucleation stage, which might become much more complex than that of the single-component nanocrystals.
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It is difficult to keep the balance of high quality and high yield for graphene quantum dots (GQDs). Because the quality is uncontrollable during cutting large 2D nanosheets to small 0D nanodots by top-down methods and the yield is low for GQDs with high quality obtained from bottom-up strategy. Here, aphanitic graphite (AG), a low-cost graphite contains a large amount of small graphite nanocrystals with size of about 10 nm is used as the precursor of graphene oxide quantum dots (GO-QDs) for the first time. GO-QDs with high yield and high quality were successfully obtained directly by liquid phase exfoliating AG without high strength cutting. The yield of these GO-QDs can reach up to 40 wt. %, much higher than that obtained from flake graphite (FG) precursor (less than 10 wt. %). The size of GO-QDs can be controlled in 2-10 nm. The average thickness of GO-QDs is about 3 nm, less than 3 layer of graphene sheet. Graphene quantum dots (GQDs) with different surface properties can be easily obtained by simple hydrothermal treatment of GO-QDs, which can be used as highly efficient fluorescent probe. Developing AG as precursor for GQDs offers a way to produce GQDs in a low-cost, highly effective and scalable manner.