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2.
Int Immunopharmacol ; 134: 112258, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38744178

RESUMEN

Ferroptosis, a form of regulated cell death (RCD), exhibits distinct characteristics such as iron-dependence and lipid peroxidation accumulation (ROS), setting it apart from other types of cell death like apoptosis and necrosis. Its role in cancer biology is increasingly recognized, particularly its potential interaction with tumor microenvironment (TME) and CD8 T cells in cancer immunotherapy. However, the impact of ferroptosis on TME cell infiltration remains unclear. In this study, we conducted unsupervised clustering analysis on patient data from public databases, identifying three ferroptosis patterns with distinct TME cell infiltration characteristics: immune-inflamed, immune-excluded, and immune-desert phenotypes. We developed a ferroptosis score based on differentially expressed genes (DEGs) among these patterns, which correlated with various biological features including chemotherapy-resistance and immune cells infiltration. Despite patients with high ferroptosis scores exhibiting worse prognosis, they showed increased likelihood of benefiting from immunotherapy. Our findings highlight the importance of ferroptosis-related patterns in understanding TME cell infiltration and suggest novel strategies for drug combinations and immune-related therapies.


Asunto(s)
Neoplasias Colorrectales , Ferroptosis , Microambiente Tumoral , Ferroptosis/genética , Humanos , Microambiente Tumoral/inmunología , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Inmunoterapia/métodos , Pronóstico , Resistencia a Antineoplásicos/genética
3.
ACS Nano ; 18(14): 10008-10018, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38551183

RESUMEN

Two-dimensional (2D) heterojunction nanomaterials offer exceptional physicochemical and catalytic properties, thanks to their special spatial electronic structure. However, synthesizing morphologically uniform 2D platinum (Pt)-based metallic nanomaterials with diverse crystalline phases remains a formidable challenge. In this study, we have achieved the successful synthesis of advanced 2D platinum-tellurium heterojunction nanosheet assemblies (Ptx-PtTe2 HJNSAs, x = 0, 1, 2), seamlessly integrating both trigonal PtTe2 (t-PtTe2) and cubic Pt (c-Pt) phases. By enabling efficient electron transport and leveraging the specific electron density present at the heterojunction, the Pt2-PtTe2 HJNSAs/C demonstrated exceptional formic acid oxidation reaction (FAOR) activity and stability. Specifically, the specific and mass activities reached 8.4 mA cm-2 and 6.1 A mgPt-1, which are 46.7 and 50.8 times higher than those of commercial Pt/C, respectively. Impressively, aberration-corrected high-angle annular dark field scanning transmission electron microscopy (AC-HAADF-STEM) revealed a closely packed arrangement of atomic layers and a coherent intergrowth heterogeneous structure. Density functional theory (DFT) calculations further indicated that rearrangement of electronic structure occurred on the surface of Pt2-PtTe2 HJNSAs resulting in a more favorable dehydrogenation pathway and excellent CO tolerance, beneficial for performance improvement. This work inspires the targeted exploration of Pt-based nanomaterials through 2D heterostructure design, leading to an important impact on fuel cell catalysis and beyond.

4.
Front Immunol ; 15: 1295693, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38312840

RESUMEN

PSME3 plays a significant role in tumor progression. However, the prognostic value of PSME3 in pan-cancer and its involvement in tumor immunity remain unclear. We conducted a comprehensive study utilizing extensive RNA sequencing data from the TCGA (The Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) databases. Our research revealed abnormal expression levels of PSME3 in various cancer types and unveiled a correlation between high PSME3 expression and adverse clinical outcomes, especially in cancers like liver cancer (LIHC) and lung adenocarcinoma (LUAD). Functional enrichment analysis highlighted multiple biological functions of PSME3, including its involvement in protein degradation, immune responses, and stem cell regulation. Moreover, PSME3 showed associations with immune infiltration and immune cells in the tumor microenvironment, indicating its potential role in shaping the cancer immune landscape. The study also unveiled connections between PSME3 and immune checkpoint expression, with experimental validation demonstrating that PSME3 positively regulates CD276. This suggests that PSME3 could be a potential therapeutic target in immunotherapy. Additionally, we predicted sensitive drugs targeting PSME3. Finally, we confirmed in both single-factor Cox and multiple-factor Cox regression analyses that PSME3 is an independent prognostic factor. We also conducted preliminary validations of the impact of PSME3 on cell proliferation and wound healing in liver cancer. In summary, our study reveals the multifaceted role of PSME3 in cancer biology, immune regulation, and clinical outcomes, providing crucial insights for personalized cancer treatment strategies and the development of immunotherapy.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Antígenos B7 , Proliferación Celular , Bases de Datos Factuales , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/genética , Microambiente Tumoral/genética
5.
Biochem Biophys Res Commun ; 692: 149344, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38070275

RESUMEN

CD81 is a cell surface transmembrane protein of the tetraspanin family, which critically regulates signal transduction and immune response. Growing evidence has shown that CD81 plays important roles in tumorigenesis and influences immunotherapy response. Here, combining bio-informatics and functional analysis, we find that CD81 is a risk factor in lung squamous cell carcinoma (LUSC), whereas a protective factor in lung adenocarcinoma. In LUSC with high expression of CD81, the autophagy and JAK-STAT signaling pathway are activated. Meanwhile, the expression level of CD81 is negatively correlated with tumor mutational load (TMB), microsatellite instability (MSI), and neoantigen (NEO). Furthermore, patients with LUSC and high expression of CD81 do not respond to immunotherapy drugs, but can respond to chemotherapy drugs. Importantly, depletion of CD81 suppresses the proliferation of LUSC cell, and enhances the sensitivity to cisplatin. Our findings suggest that CD81 represents a potential target for cisplatin-based chemotherapy in patients with LUSC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Cisplatino , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Pulmón/patología , Tetraspanina 28/metabolismo
6.
J Am Chem Soc ; 145(28): 15393-15404, 2023 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-37429024

RESUMEN

Designing efficient formic acid oxidation reaction (FAOR) catalysts with remarkable membrane electrode assembly (MEA) performance in a direct formic acid fuel cell (DFAFC) medium is significant yet challenging. Herein, we report that the monoclinic-phased platinum-tellurium nanotrepang (m-PtTe NT) can be adopted as a highly active, selective, and stable FAOR catalyst with a desirable direct reaction pathway. The m-PtTe NT exhibits the high specific and mass activities of 6.78 mA cm-2 and 3.2 A mgPt-1, respectively, which are 35.7/22.9, 2.8/2.6, and 3.9/2.9 times higher than those of commercial Pt/C, rhombohedral-phased Pt2Te3 NT (r-Pt2Te3 NT), and trigonal-phased PtTe2 NT (t-PtTe2 NT), respectively. Simultaneously, the highest reaction tendency for the direct FAOR pathway and the best tolerance to poisonous CO intermediate can also be realized by m-PtTe NT. More importantly, even in a single-cell medium, the m-PtTe NT can display a much higher MEA power density (171.4 mW cm-2) and stability (53.2% voltage loss after 5660 s) than those of commercial Pt/C, demonstrating the great potential in operating DFAFC device. The in-situ Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy jointly demonstrate that the unique nanostructure of m-PtTe NT can effectively optimize dehydrogenation steps and inhibit the CO intermediate adsorption, as well as promote the oxidation of noxious CO intermediate, thus achieving the great improvement of FAOR activity, poisoning tolerance, and stability. Density functional theory calculations further reveal that the direct pathway is the most favorable on m-PtTe NT than r-Pt2Te3 NT and t-PtTe2 NT. The higher activation energy to produce CO and the relatively weaker binding with CO of m-PtTe NT result in the better CO tolerance. This work achieves remarkable FAOR and MEA performances of advanced Pt-based anodic catalysts for DFAFCs via a phase engineering strategy.

7.
ACS Nano ; 17(6): 5861-5870, 2023 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-36920478

RESUMEN

Thickness regulation of transition metal hydroxides/oxides nanosheets with superior catalytic properties represents a promising strategy to enhance catalytic performance, but it remains an enormous challenge to achieve precise control, especially when it comes to the ultrathin limit (several atomic layers). In this work, a facile strategy of alkylamine-confined growth is proposed for the synthesis of thickness-tunable metal hydroxide/oxide nanosheets. Specifically, ultrathin cobalt hydroxide and cobaltous oxide hybrid (Co(OH)2-CoO) nanosheets (Co-O NSs) with a thickness in the range of 2-6 nm (5-13 atomic layers) are synthesized by using alkylamines with different carbon chain lengths as the ligand to modulate vertical coordination ability. Co-O NSs with a thickness of 2 nm (Co-O NSs-2 nm) exhibit excellent oxygen evolution reaction (OER) performance with an overpotential of 278 mV at 10 mA/cm2. The maximized number of active sites including oxygen vacancies, optimal adsorption strength, and the highest electrical conductivity are considered as the potential factors contributing to the excellent OER performance of Co-O NSs-2 nm. This work holds great significance for the precise thickness-tunable synthesis of transition metal layered hydroxide nanosheets with modulated and improved catalytic performance.

8.
Front Oncol ; 13: 1287808, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38213838

RESUMEN

Disulfidptosis is a novel mechanism underlying actin-cytoskeleton-associated cell death, but its function in colorectal cancer (CRC) is still elusive. In this study, we investigated the potential role of Disulfidptosis-Related Long Non-Coding RNAs (DRLs) as prognostic indicators in CRC. Through transcriptome data from TCGA CRC cases, we identified 44 prognosis-correlated DRLs by Univariate Cox Regression Analysis and observed a differential expression pattern of these DRLs between CRC and normal tissues. Consensus clustering analysis based on DRL expression led to subgroup classification of CRC patients with distinct molecular fingerprints, accompanied by a superior survival outcome in cluster 2. We are encouraged to develop a score model incorporating 12 key DRLs to predict patient outcomes. Notably, this model displayed more reliable accuracy than other predictive indicators since DRLs are intimately related to tumor immune cell infiltration, suggesting a considerable potential of our DRL-score model for tumor therapy. Our data offered a valuable insight into the prognostic significance of DRLs in CRC and broke a new avenue for tumor prognosis prediction.

9.
Front Immunol ; 14: 1338244, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38250074

RESUMEN

Background: Glioma is the prevailing malignant intracranial tumor, characterized by an abundance of macrophages. Specifically, the infiltrating macrophages often display the M2 subtype and are known as tumor-associated macrophages (TAMs). They have a critical role in promoting the oncogenic properties of tumor cells. Interleukin-4-induced-1 (IL4I1) functions as an L-phenylalanine oxidase, playing a key part in regulating immune responses and the progression of various tumors. However, there is limited understanding of the IL4I1-mediated cross-talk function between TAMs and glioma cell in the glioma microenvironment. Methods: TCGA, GTEx, and HPA databases were applied to assess the IL4I1 expression, clinical characteristics, and prognostic value of pan-cancer. The link between IL4I1 levels and the prognosis, methylation, and immune checkpoints (ICs) in gliomas were explored through Kaplan-Meier curve, Cox regression, and Spearman correlation analyses. The IL4I1 levels and their distribution were investigated by single-cell analysis and the TIMER 2 database. Additionally, validation of IL4I1 expression was performed by WB, RT-qPCR, IHC, and IF. Co-culture models between glioma cells and M2-like macrophages were used to explore the IL4I1-mediated effects on tumor growth, invasion, and migration of glioma cells. Moreover, the function of IL4I1 on macrophage polarization was evaluated by ELISA, RT-qPCR, WB, and siRNA transfection. Results: Both transcriptome and protein levels of IL4I1 were increased obviously in various tumor types, and correlated with a dismal prognosis. Specifically, IL4I1 was implicated in aggressive progression and a dismal prognosis for patients with glioma. A negative association was noticed between the glioma grade and DNA promoter methylation of IL4I1. Enrichment analyses in glioma patients suggested that IL4I1 was linked to cytokine and immune responses, and was positively correlated with ICs. Single-cell analysis, molecular experiments, and in vitro assays showed that IL4I1 was significantly expressed in TAMs. Importantly, co-culture models proved that IL4I1 significantly promoted the invasion and migration of glioma cells, and induced the polarization of M2-like macrophages. Conclusion: IL4I1 could be a promising immunotherapy target for selective modulation of TAMs and stands as a novel macrophage-related prognostic biomarker in glioma.


Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Macrófagos , Glioma/genética , Glioma/terapia , Macrófagos Asociados a Tumores , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Inmunoterapia , Microambiente Tumoral , L-Aminoácido Oxidasa
10.
Micromachines (Basel) ; 13(12)2022 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-36557398

RESUMEN

Amorphous InGaZnO thin film transistors (a-IGZO TFTs) with double-stacked channel layers (DSCL) were quite fit for ultraviolet (UV) light detection, where the best DSCL was prepared by the depositions of oxygen-rich (OR) IGZO followed by the oxygen-deficient (OD) IGZO films. We investigated the influences of oxygen partial pressure (PO) for DSCL-TFTs on their sensing abilities by experiments as well as Technology Computer Aided Design (TCAD) simulations. With the increase in PO values for the DSCL depositions, the sensing parameters, including photogenerated current (Iphoto), sensitivity (S), responsivity (R), and detectivity (D*) of the corresponding TFTs, apparently degraded. Compared with PO variations for the OR-IGZO films, those for the OD-IGZO depositions more strongly influenced the sensing performances of the DSCL-TFT UV light detectors. The TCAD simulations showed that the variations of the electron concentrations (or oxygen vacancy (VO) density) with PO values under UV light illuminations might account for these experimental results. Finally, some design guidelines for DSCL-TFT UV light detectors were proposed, which might benefit the potential applications of these novel semiconductor devices.

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