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1.
Biochim Biophys Acta Mol Basis Dis ; 1870(6): 167230, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38734322

RESUMEN

The exploration of the complex mechanisms of cancer immunotherapy is rapidly evolving worldwide, and our focus is on the interaction of hepatocellular carcinoma (HCC) with immune checkpoint inhibitors (ICIs), particularly as it relates to the regulatory role of the gut microbiome. An important basis for the induction of immune responses in HCC is the presence of specific anti-tumor cells that can be activated and reinforced by ICIs, which is why the application of ICIs results in sustained tumor response rates in the majority of HCC patients. However, mechanisms of acquired resistance to immunotherapy in unresectable HCC result in no long-term benefit for some patients. The significant heterogeneity of inter-individual differences in the gut microbiome in response to treatment with ICIs makes it possible to target modulation of specific gut microbes to assist in augmenting checkpoint blockade therapies in HCC. This review focuses on the complex relationship between the gut microbiome, host immunity, and HCC, and emphasizes that manipulating the gut microbiome to improve response rates to cancer ICI therapy is a clinical strategy with unlimited potential.

2.
Int J Mol Sci ; 25(8)2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38673832

RESUMEN

Phytophthora root rot is a devastating disease of soybean caused by Phytophthora sojae. However, the resistance mechanism is not yet clear. Our previous studies have shown that GmAP2 enhances sensitivity to P. sojae in soybean, and GmMYB78 is downregulated in the transcriptome analysis of GmAP2-overexpressing transgenic hairy roots. Here, GmMYB78 was significantly induced by P. sojae in susceptible soybean, and the overexpressing of GmMYB78 enhanced sensitivity to the pathogen, while silencing GmMYB78 enhances resistance to P. sojae, indicating that GmMYB78 is a negative regulator of P. sojae. Moreover, the jasmonic acid (JA) content and JA synthesis gene GmAOS1 was highly upregulated in GmMYB78-silencing roots and highly downregulated in overexpressing ones, suggesting that GmMYB78 could respond to P. sojae through the JA signaling pathway. Furthermore, the expression of several pathogenesis-related genes was significantly lower in GmMYB78-overexpressing roots and higher in GmMYB78-silencing ones. Additionally, we screened and identified the upstream regulator GmbHLH122 and downstream target gene GmbZIP25 of GmMYB78. GmbHLH122 was highly induced by P. sojae and could inhibit GmMYB78 expression in resistant soybean, and GmMYB78 was highly expressed to activate downstream target gene GmbZIP25 transcription in susceptible soybean. In conclusion, our data reveal that GmMYB78 triggers soybean sensitivity to P. sojae by inhibiting the JA signaling pathway and the expression of pathogenesis-related genes or through the effects of the GmbHLH122-GmMYB78-GmbZIP25 cascade pathway.


Asunto(s)
Ciclopentanos , Resistencia a la Enfermedad , Regulación de la Expresión Génica de las Plantas , Glycine max , Oxilipinas , Phytophthora , Enfermedades de las Plantas , Proteínas de Plantas , Factores de Transcripción , Glycine max/genética , Glycine max/microbiología , Glycine max/parasitología , Glycine max/metabolismo , Phytophthora/patogenicidad , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/parasitología , Enfermedades de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Plantas Modificadas Genéticamente , Raíces de Plantas/microbiología , Raíces de Plantas/genética , Raíces de Plantas/parasitología , Raíces de Plantas/metabolismo
3.
Sci Rep ; 14(1): 9764, 2024 04 29.
Artículo en Inglés | MEDLINE | ID: mdl-38684762

RESUMEN

SPTBN2 is a protein-coding gene that is closely related to the development of malignant tumors. However, its prognostic value and biological function in pan-cancer, especially pancreatic cancer (PAAD), have not been reported. In the present study, a novel exploration of the value and potential mechanism of SPTBN2 in PAAD was conducted using multi-omics in the background of pan-cancer. Via various database analysis, up-regulated expression of SPTBN2 was detected in most of the tumor tissues examined. Overexpression of SPTBN2 in PAAD and kidney renal clear cell cancer patients potentially affected overall survival, disease-specific survival, and progression-free interval. In PAAD, SPTBN2 can be used as an independent factor affecting prognosis. Mutations and amplification of SPTBN2 were detected, with abnormal methylation of SPTBN2 affecting its expression and the survival outcome of PAAD patients. Immunoassay results demonstrate that SPTBN2 was a potential biomarker for predicting therapeutic response in PAAD, and may influence the immunotherapy efficacy of PAAD by regulating levels of CD8 + T cells and neutrophil infiltration. Results from an enrichment analysis indicated that SPTBN2 may regulate the development of PAAD via immune pathways. Thus, SPTBN2 is a potential prognostic biomarker and immunotherapy target based on its crucial role in the development of PAAD.


Asunto(s)
Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Pronóstico , Espectrina/metabolismo , Espectrina/genética , Masculino , Femenino , Mutación , Metilación de ADN , Multiómica
4.
BMC Genomics ; 25(1): 250, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38448802

RESUMEN

BACKGROUND: Immunotherapy is a practical therapeutic approach in breast cancer (BRCA), and the role of FLI1 in immune regulation has gradually been unveiled. However, the specific role of FLI1 in BRCA was conflicted; thus, additional convincing evidence is needed. METHODS: We explored the upstream regulation of FLI1 expression via summary data-based Mendelian randomization (SMR) analysis and ncRNA network construction centering on FLI1 using BRCA genome-wide association study (GWAS) summary data with expression quantitative trait loci (eQTLs) and DNA methylation quantitative trait loci (mQTLs) from the blood and a series of in silico analyses, respectively. We illuminated the downstream function of FLI1 in immune regulation by integrating a series of analyses of single-cell RNA sequence data (scRNA-seq). RESULTS: We verified a causal pathway from FLI1 methylation to FLI1 gene expression to BRCA onset and demonstrated that FLI1 was downregulated in BRCA. FLI1, a transcription factor, served as myeloid and T cells' communication regulator by targeting immune-related ligands and receptor transcription in BRCA tissues. We constructed a ceRNA network centering on FLI1 that consisted of three LncRNAs (CKMT2-AS1, PSMA3-AS1, and DIO3OS) and a miRNA (hsa-miR-324-5p), and the expression of FLI1 was positively related to a series of immune-related markers, including immune cell infiltration, biomarkers of immune cells, and immune checkpoints. CONCLUSION: Low-methylation-induced or ncRNA-mediated downregulation of FLI1 is associated with poor prognosis, and FLI1 might regulate the tumor immune microenvironment via a cell-type-specific target genes manner in BRCA.


Asunto(s)
MicroARNs , Neoplasias , Humanos , Forma Mitocondrial de la Creatina-Quinasa , Regulación de la Expresión Génica , Estudio de Asociación del Genoma Completo , MicroARNs/genética , Sitios de Carácter Cuantitativo , Factores de Transcripción , Microambiente Tumoral/genética
5.
Chin J Integr Med ; 30(5): 468-479, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38329654

RESUMEN

Activation of the NOD-like receptor protein 3 (NLRP3) inflammasome signaling pathway is an important mechanism underlying myocardial pyroptosis and plays an important role in inflammatory damage to myocardial tissue in patients with cardiovascular diseases (CVDs), such as diabetic cardiomyopathy, ischemia/reperfusion injury, myocardial infarction, heart failure and hypertension. Noncoding RNAs (ncRNAs) are important regulatory factors. Many Chinese medicine (CM) compounds, including their effective components, can regulate pyroptosis and exert myocardium-protecting effects. The mechanisms underlying this protection include inhibition of inflammasome protein expression, Toll-like receptor 4-NF-κB signal pathway activation, oxidative stress, endoplasmic reticulum stress (ERS), and mixed lineage kinase 3 expression and the regulation of silent information regulator 1. The NLRP3 protein is an important regulatory target for CVD prevention and treatment with CM. Exploring the effects of the interventions mediated by CM and the related mechanisms provides new ideas and perspectives for CVD prevention and treatment.


Asunto(s)
Enfermedades Cardiovasculares , Inflamasomas , Medicina Tradicional China , Piroptosis , Animales , Humanos , Enfermedades Cardiovasculares/metabolismo , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
6.
Environ Res ; 248: 118271, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38262515

RESUMEN

Antibiotics and antibiotic resistance genes (ARGs), known as emerging contaminants, have raised widespread concern due to their potential environmental and human health risks. In this study, a conventional bioretention cell (C-BRC) and three modified bioretention cells with biochar (BC-BRC), microbial fuel cell coupled/biochar (EBC-BRC) and zero-valent iron/biochar (Fe/BC-BRC) were established and two antibiotics, namely sulfamethoxazole (SMX) and tetracycline (TC), were introduced into the systems in order to thoroughly investigate the co-stress associated with the long-term removal of pollutants, dynamics of microbial community, ARGs and functional genes in wastewater treatment. The results demonstrated that the SMX and TC co-stress significantly inhibited the removal of total nitrogen (TN) (C-BRC: 37.46%; BC-BRC: 41.64%; EBC-BRC: 55.60%) and total phosphorous (TP) (C-BRC: 53.11%; BC-BRC: 55.36%; EBC-BRC: 62.87%) in C-BRC, BC-BRC and EBC-BRC, respectively, while Fe/BC-BRC exhibited profoundly stable and high removal efficiencies (TN: 89.33%; TP: 98.36%). Remarkably, greater than 99% removals of SMX and TC were achieved in three modified BRCs compared with C-BRC (SMX: 30.86 %; TC: 59.29%). The decreasing absolute abundances of denitrifying bacteria and the low denitrification functional genes (nirK: 2.80 × 105-5.97 × 105 copies/g; nirS: 7.22 × 105-1.69 × 106 copies/g) were responsible for the lower TN removals in C-BRC, BC-BRC and EBC-BRC. The amendment of Fe/BC successfully detoxified SMX and TC to functional bacteria. Furthermore, the co-stress of antibiotics stimulated the propagation of ARGs (sulI, sulII, tetA and tetC) in substrates of all BRCs and only Fe/BC-BRC effectively reduced all the ARGs in effluent by an order of magnitude. The findings contribute to developing robust ecological wastewater treatment technologies to simultaneously remove nutrients and multiple antibiotics.


Asunto(s)
Antibacterianos , Carbón Orgánico , Microbiota , Humanos , Antibacterianos/farmacología , Sulfametoxazol , Hierro , Genes Bacterianos , Tetraciclina/farmacología , Farmacorresistencia Microbiana/genética , Bacterias
7.
Aging (Albany NY) ; 16(3): 2249-2272, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38289597

RESUMEN

The role of gut microbes (GM) and their metabolites in colorectal cancer (CRC) development has attracted increasing attention. Several studies have identified specific microorganisms that are closely associated with CRC occurrence and progression, as well as key genes associated with gut microorganisms. However, the extent to which gut microbes-related genes can serve as biomarkers for CRC progression or prognosis is still poorly understood. This study used a bioinformatics-based approach to synthetically analyze the large amount of available data stored in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Through this analysis, this study identified two distinct CRC molecular subtypes associated with GM, as well as CRC markers related to GM. In addition, these new subtypes exhibit significantly different survival outcomes and are characterized by distinct immune landscapes and biological functions. Gut microbes-related biomarkers (GMRBs), IL7 and BCL10, were identified and found to have independent prognostic value and predictability for immunotherapeutic response in CRC patients. In addition, a systematic collection and review of prior research literature on GM and CRC provided additional evidence to support these findings. In conclusion, this paper provides new insights into the underlying pathological mechanisms by which GM promotes the development of CRC and suggests potentially viable solutions for individualized prevention, screening, and treatment of CRC.


Asunto(s)
Neoplasias Colorrectales , Microbioma Gastrointestinal , Humanos , Biomarcadores , Biología Computacional , Bases de Datos Factuales , Neoplasias Colorrectales/genética , Pronóstico
8.
J Ethnopharmacol ; 324: 117770, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38219877

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: To explore the differences in the anti-inflammatory efficacy and mechanisms of the Miao medicine, both raw and after processing, using the "sweat soaking method" of Radix Wikstroemia indica (RWI). AIM OF THE STUDY: The purpose of this study was to explore the differences in the anti-inflammatory efficacy and mechanism of action before and after the processing of the Miao medicine (RWI) using the "sweat soaking method." MATERIALS AND METHODS: Network pharmacology technology was used to construct the "drug-component target-pathway-disease" network, and the main anti-inflammatory pathways of RWI were identified. Rat models of collagen-induced arthritis were established. The changes in body weight, swelling rate of the foot pad and ankle joint, arthritis index, thymus index, spleen index, pathological changes of the ankle joint, and the content of inflammatory cytokines (IL-1ß, IL-2, IL-6, IL-10, TNF-α, and NO) were used as indices to evaluate the effect of RWI on rats with collagen-induced arthritis before and after its processing. Plasma and urine samples were collected from the rats, and the potential biomarkers of, and metabolic pathways underlying the anti-inflammatory effects of RWI before and after processing were identified using 1H-Nuclear magnetic resonance metabolomics combined with a multivariate statistical analysis. RESULTS: Eleven key anti-inflammatory targets of IL6, IL-1ß, TNF, ALB, AKT1, IFNG, INS, STAT3, EGFR, TP53, and SRC were identified by network pharmacology. The PI3K-Akt signaling pathway, steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism, tryptophan metabolism, and other pathways were mainly involved in these effects. Pharmacodynamic studies found that both raw and processed RWI products downregulated inflammatory factors in rats with collagen-induced arthritis and alleviated the pathological changes. A total of 41 potential pathways for the anti-inflammatory effects of raw RWI products and 36 potential pathways for the anti-inflammatory effects of processed RWI products were identified by plasma and urine metabolomics. The common pathways of network pharmacology and metabolomics were steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism, and tryptophan metabolism. CONCLUSIONS: The anti-inflammatory effect of RWI was mainly related to the regulation of steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism, and tryptophan metabolism. Finally, the "sweat soaking method" enhanced the anti-inflammatory effect of RWI.


Asunto(s)
Artritis Experimental , Medicamentos Herbarios Chinos , Wikstroemia , Ratas , Animales , Artritis Experimental/inducido químicamente , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patología , Sudor/química , Fosfatidilinositol 3-Quinasas , Triptófano , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/análisis , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Arginina , Esteroides , Hormonas , Prolina
9.
Sensors (Basel) ; 23(21)2023 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-37960618

RESUMEN

Rubidium laser optically pumped magnetometers (OPMs) are widely used magnetic sensors based on the Zeeman effect, laser pumping, and magnetic resonance principles. They measure the magnetic field by measuring the magnetic resonance signal passing through a rubidium atomic gas cell. The quality of the magnetic resonance signal is a necessary condition for a magnetometer to achieve high sensitivity. In this research, to obtain the best magnetic resonance signal of rubidium laser OPMs in the Earth's magnetic field intensity, the experiment system of rubidium laser OPMs is built with a rubidium atomic gas cell as the core component. The linewidth and amplitude ratio (LAR) of magnetic resonance signals is utilized as the optimization objective function. The magnetic resonance signals of the magnetometer experiment system are experimentally measured for different laser frequencies, radio frequency (RF) intensities, laser powers, and atomic gas cell temperatures in a background magnetic field of 50,765 nT. The experimental results indicate that optimizing these parameters can reduce the LAR by one order of magnitude. This shows that the optimal parameter combination can effectively improve the sensitivity of the magnetometer. The sensitivity defined using the noise spectral density measured under optimal experimental parameters is 1.5 pT/Hz1/2@1 Hz. This work will provide key technical support for rubidium laser OPMs' product development.

10.
Nat Commun ; 14(1): 5583, 2023 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-37696902

RESUMEN

Azulene-based conjugated systems are of great interests due to their unusual structures and photophysical properties. Incorporation of a transition metal into azulene skeleton presents an intriguing opportunity to combine the dπ-pπ and pπ-pπ conjugated properties. No such metallaazulene skeleton however has been reported to date. Here, we describe our development of an efficient [5 + 2] annulation reaction to rapid construction of a unique metal-containing [5-5-7] scaffold, termed metalla-dual-azulene (MDA), which includes a metallaazulene and a metal-free organic azulene intertwined by sharing the tropylium motif. The two azulene motifs in MDA exhibit distinct reactivities. The azulene motif readily undergoes nucleophilic addition, leading to N-, O- and S-substituted cycloheptanetrienyl species. Demetalation of the metallaazulene moiety occurs when it reacts with nBu4NF, which enables highly selective recognition of fluoride anion and a noticeable color change. The practical [5 + 2] annulation methodology, facile functional-group modification, high and selective fluoride detection make this new π-conjugated polycyclic system very suitable for potential applications in photoelectric and sensing materials.

11.
Bioresour Technol ; 385: 129442, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37399958

RESUMEN

The study aimed to investigate the pretreatment characteristics of food waste (FW) by Bacillus licheniformis and Bacillus oryzaecorticis, and to determine the contribution of microbial hydrolysis in the structure of fulvic acid (FA) and humic acid (HA). FW was pretreated with Bacillus oryzaecorticis (FO) and Bacillus licheniformis (FL), and the resulting solution was heated to synthesize humus. The results showed that the acidic substances produced by microbial treatments led to a decrease in pH. In addition, Bacillus oryzaecorticis degraded starch and released a large amount of reducing sugar, providing OH and COOH to FA molecules. Bacillus licheniformis showed a positive effect on the HA structure, which had higher OH, CH3 and aliphatics. FO is more beneficial to retain OH and COOH, while FL is more beneficial to retain amino and aliphatics. This study provided evidence for the application of Bacillus licheniformis and Bacillus oryzaecorticis in waste management.


Asunto(s)
Bacillus licheniformis , Bacillus , Eliminación de Residuos , Suelo , Alimentos , Bacillus/metabolismo , Sustancias Húmicas
12.
Environ Res ; 236(Pt 1): 116744, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37500044

RESUMEN

Accurate assessment of grassland soil erosion before and after grazing exclusion and revealing its driving mechanism are the basis of grassland risk management. In this study, the long-term soil erosion in Ningxia grassland was simulated by integrating and calibrating the transport limited sediment delivery (TLSD) function with the revised universal soil loss equation (RUSLE) model. The differential mechanisms of soil loss were explored using the GeoDetector method, and the relative effects of precipitation changes (PC) and human activities (HA) on grassland soil erosion were investigated using double mass curves. The measured sediment discharges from six hydrological stations verified that the RUSLE-TLSD model could reliably simulate water erosion in Ningxia. From 1988 to 2018, the water erosion rate of grassland in Ningxia ranged from 74.98 to 14.98 t⋅ha-1⋅a-1, showing an overall downward trend. July to September is the period with the highest of water erosion. The slope is the dominant factor influencing the spatial distribution of water erosion. After grazing exclusion, the net water erosion rate in Ningxia grassland and sub-regions decreased significantly. The double mass curves results show that human activities were the main driver of net erosion reduction. The focus of water erosion control in Ningxia is to control soil erosion in different terrains and protect grassland with slopes greater than 10°.

13.
Acta Cardiol ; 78(6): 703-712, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37103119

RESUMEN

BACKGROUND: The main purpose of this study was to establish an ideal arrhythmia model using isoproterenol and explore its mechanism. METHODS: Fifty healthy male SD rats were randomly divided into the following groups: control (CON), subcutaneous injection (SC; 5 mg/kg ISO for 2 consecutive days), intraperitoneal injection (IP; ISO 5 mg/kg for 2 consecutive days), 2 + 1 (5 mg/kg ISO by SC for 2 consecutive days and then 3 mg/kg ISO by IP for 1 day), and 6 + 1 (5 mg/kg ISO by SC for 6 consecutive days and then 3 mg/kg ISO by IP for 1 day). Electrocardiograms (ECGs) were recorded using a BL-420F system, and the pathological changes in myocardial tissue were observed by HE and Masson staining. The serum cTnI, TNF-α, IL-6, and IL-1ß levels were detected by ELISA, and serum CK, LDH and oxidative stress-related indicators were detected with an automatic biochemical analyser. RESULTS: The cardiomyocytes of the rats belonging to the CON group were normal, whereas those of the rats in the other groups, particularly the 6 + 1 group, showed signs of disorder, unclear borders, and lysis and necrosis. The incidence of arrhythmia, arrhythmia score, and levels of serum myocardial enzymes, troponin, and some inflammatory factors were higher in the 2 + 1 and 6 + 1 groups than in the single injection group (p < 0.01 or p < 0.05). The indicator levels found for the 6 + 1 group were generally higher than those found for the 2 + 1 group (p < 0.01), and the 6 + 1 group exhibited a lower SOD level and higher MDA and NO levels compared with the CON group (p < 0.01 or p < 0.05). CONCLUSION: The combined mode of ISO injection (SC with IP) was more likely to induce arrhythmia than a single ISO injection. The "6 + 1" method of ISO injection can establish a more stable arrhythmia model and cardiomyocyte damage induced by oxidative stress and inflammation was an important mechanism.


Asunto(s)
Cardiotónicos , Miocardio , Humanos , Ratas , Masculino , Animales , Isoproterenol/farmacología , Cardiotónicos/farmacología , Cardiotónicos/uso terapéutico , Ratas Sprague-Dawley , Miocardio/patología , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/tratamiento farmacológico
14.
BMC Med Genomics ; 15(1): 242, 2022 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-36419120

RESUMEN

BACKGROUND: MYCN amplification (MNA) has been proved to be related to poor prognosis in neuroblastoma (NBL), but the MYCN-related immune signatures and genes remain unclear. METHODS: Enrichment analysis was used to identify the significant enrichment pathways of differentially expressed immune-related genes (DEIRGs). Weight gene coexpression network analysis (WGCNA) was applied to reveal the correlation between these DEIRGs and MYCN status. Univariate and multivariate Cox analyses were used to construct risk model. The relevant fractions of immune cells were evaluated by CIBERSORT and single-sample gene set enrichment analysis (ssGSEA). RESULTS: Five genes, including CHGA, PTGER1, SHC3, PLXNC1, and TRIM55 were enrolled into the risk model. Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curve showed that our model performed well in predicting the outcomes of NBL (3-years AUC = 0.720, 5-year AUC = 0.775, 10-years AUC = 0.782), which has been validated in the GSE49711 dataset and the E-MTAB-8248 dataset. By comparing with the tumor immune dysfunction and exclusion (TIDE) and tumor inflammation signature (TIS), we further proved that our model is reliable. Univariate and multivariate Cox regression analyses indicated that the risk score, age, and MYCN can serve as independent prognostic factors in the E-MATB-8248. Functional enrichment analysis showed the DEIRGs were enriched in leukocyte adhesion-related signaling pathways. Gene set enrichment analysis (GSEA) revealed the significantly enriched pathways of the five MYCN-related DEIRGs. The risk score was negatively correlated with the immune checkpoint CD274 (PD-L1) but no significant difference with the TMB. We also confirmed the prognostic value of our model in predicting immunotherapeutics. CONCLUSION: We constructed and verified a signature based on DEIRG that related to MNA and predicted the survival of NBL based on relevant immune signatures. These findings could provide help for predicting prognosis and developing immunotherapy in NBL.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Neuroblastoma , Humanos , Biomarcadores de Tumor/genética , Proteína Proto-Oncogénica N-Myc/genética , Neuroblastoma/genética , Pronóstico
15.
Angew Chem Int Ed Engl ; 61(48): e202211734, 2022 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-36189860

RESUMEN

The structural design and tuning of properties of metallaaromatics are crucial in materials and energy science. Herein, we describe the rapid synthesis of tetracyclic metallaaromatics containing quinoline and pentalene motifs fused by a metal-bridged fragment. These unique compounds display remarkably broad absorption, enabling for the first time the absorption of metallaaromatics to reach the second near-infrared (NIR-II) bio-window. The formation of osmaquinoline unit involves an unconventional C(sp2 )-C(sp3 ) coupling promoted by AgBF4 to achieve [3+3] cycloaddition. The introduction of cyclic dπ -pπ conjugation and extension of the aromatic π-framework can effectively shrink the HOMO-LUMO gap, thus broadening the absorption window. The considerable photothermal conversion efficiency (PCE) in both the NIR-I and NIR-II windows, the high photothermal stability and the excellent electrochemical behavior suggest many potential applications of these condensed metallaquinolines.

16.
ACS Appl Mater Interfaces ; 14(31): 36258-36267, 2022 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-35881933

RESUMEN

Indium tin oxide (ITO) thin films suffer from poor chemical stability at high temperatures because of the instability of point defects and structural variations. An interface design strategy was proposed herein to improve this situation, where a robust ITO-based thin film with a column-layer structure was fabricated. Three types of column-layer ITO thin films were fabricated via magnetron sputtering. By tuning the interfaces, we controlled the effective mass and weighted mobility, enhancing the electrical conductivity (2.17 × 106 S m-1) and power factor (1138 µW m-1 K-2). The crack propagation path was prolonged because of the profuse interfaces between the columns and layers in the alternate thin films. Thus, enhanced nanohardness (16.5 GPa) was obtained. The structural evolution and performance of the column-layer ITO thin films annealed under different conditions were investigated. The atoms were restricted by the profuse interfaces, resulting in high-temperature stability. The results demonstrate that the interface design of ITO thin films can efficiently modify the stability of conductive ceramics over a wide temperature range, which has significant potential for applications in microdevices and aero engines.

17.
Exp Cell Res ; 418(1): 113244, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-35697078

RESUMEN

PLIN2 has been found to be dysregulated in several human malignancies, which influences cancer progression. However, the roles of PLIN2 in regulating hepatocellular carcinoma (HCC) progression are still unclear. Here, we revealed that PLIN2 was frequently upregulated in HCC cells and tissues, and increased PLIN2 expression was associated with poor prognosis outcomes in HCC. In HCC cells, overexpressing PLIN2 promoted cell proliferation, PLIN2-deficiency inhibited cell vitality. Mechanistically, silencing of PLIN2 expression downregulated hypoxia inducible factor 1-α (HIF1α) expression and this downregulation in turn inhibited the targeting genes of HIF1α. Furthermore, we found that PLIN2 stabilized and retarded the degradation of the HIF1α through autophagy-lysosomal pathway by inhibiting AMPK/ULK1. Collectively, we clarified the carcinogenic role of PLIN2 in HCC and suggested a prognostic biomarker for diagnosis and clinical therapy in the future.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Autofagia/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Hepáticas/patología , Perilipina-2/metabolismo
18.
Phys Chem Chem Phys ; 24(11): 6905-6914, 2022 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-35253825

RESUMEN

The research on the stable thermoelectric properties and contact interface of high-precision thin-film thermocouples lags far behind the demand. In this study, a zinc-rich Al-doped ZnO (AZO) thin film was fabricated, in which the carriers were mainly donated by the Al dopant, and the oxygen defects migrated together, forming cage defects. Then, an indium tin oxide (ITO)/AZO thin-film thermocouple was prepared. It had a special temperature-dependent voltage curve due to the effects of cage defects on the thermoelectric properties of the AZO thin film and interfacial electron diffusion. When the zinc atoms in the cage defects were excited after annealing, a linear relationship between the temperature and voltage was obtained. The Seebeck coefficient of the thermocouple was constant at 168 µV K-1 over the entire measured temperature range. In addition, the calculated error of the thermocouple was lower than 1% from 50 °C to 500 °C, showing good repeatability. These results showed that defect engineering could effectively be used to improve the temperature range stability of thermoelectric materials and optimize the precision of thin-film thermocouples.

19.
Artículo en Inglés | MEDLINE | ID: mdl-35111237

RESUMEN

Cardiorenal syndrome (CRS), a clinical syndrome involving multiple pathological mechanisms, exhibits high morbidity and mortality. According to the primary activity of the disease, CRS can be divided into cardiorenal syndrome (type I and type II), renal heart syndrome (type III and type IV), and secondary heart and kidney disease (type V). The renin-angiotensin-aldosterone system (RAAS) is an important humoral regulatory system of the body that exists widely in various tissues and organs. As a compensatory mechanism, the RAAS is typically activated to participate in the regulation of target organ function. RAAS activation plays a key role in the pathogenesis of CRS. The RAAS induces the onset and development of CRS by mediating oxidative stress, uremic toxin overload, and asymmetric dimethylarginine production. Research on the mechanism of RAAS-induced CRS can provide multiple intervention methods that are of great significance for reducing end-stage organ damage and further improving the quality of life of patients with CRS.


Asunto(s)
Síndrome Cardiorrenal , Insuficiencia Cardíaca , Humanos , Riñón , Calidad de Vida , Sistema Renina-Angiotensina
20.
Phys Chem Chem Phys ; 24(10): 6163-6168, 2022 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-35226019

RESUMEN

The long-term precise high-temperature measurement of thin-film thermocouples (TFTCs) has attracted attention due to the capability of instantaneous temperature detection. However, related technologies have seen slow development, and there is no one standard TFTC yet. Here, we focus on a new strategy of reducing alloys for the easy preparation and performance enhancement of TFTCs via nanostructure and interface design. To this end, we fabricated a platinum/iridium (Pt/Ir) pure-element TFTC with a well matched interface and few defects, which demonstrated excellent long-term service stability over a high-temperature range. The corresponding polynomial fitting coefficients were ≥0.99999, indicating the accurate acquisition of temperature data. A reduced deviation (<0.21%) between three calibration cycles was obtained over a wide temperature range of 300 °C to 1000 °C, which is better than the maximum precision of a standard wire thermocouple. Superior properties are achieved because of the resulting fewer defects in the Pt and Ir thin films with highly preferential orientation along the (111) plane. The results indicate that our Pt/Ir TFTCs have significant potential for application in many domains such as thermal detection, microelectronics and aero-engines.

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