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While ferroptosis shows promise in anti-cancer strategy, the molecular mechanisms behind this process remain poorly understood. Our research aims to highlight the regulation of radiotherapy-induced ferroptosis in non-small cell lung cancer (NSCLC) via the NRF2/PHKG2 axis-mediated mechanism. To identify ferroptosis-associated genes associated with radioresistance in NSCLC, this study employed high-throughput transcriptome sequencing and Lasso risk regression analysis. Clinical samples were analyzed to confirm PHKG2 expression changes before and after radiotherapy. The study further examined ferritinophagy-related factors, intracellular iron levels, mitochondrial function, and ferroptosis in NSCLC cells undergoing radiation exposure to explore the effect of PHKG2 on radiosensitivity or radioresistance. The research also demonstrated the transcriptional inhibition of PHKG2 by NRF2 and created in situ transplantation tumor models of NSCLC to examine the role of NRF2/PHKG2 axis in NSCLC radiosensitivity and resistance in vivo. The Lasso risk regression model that incorporated ferroptosis-associated genes effectively predicted the prognosis of patients with NSCLC. Radiotherapy-sensitive tissues exhibited an increased expression of PHKG2. Overexpression of PHKG2 led to elevated intracellular iron levels by promoting ferritinophagy and increased mitochondrial stress-dependent ferroptosis induced by radiotherapy. PHKG2 transcription repression was achieved through NRF2. The FAGs-Lasso risk regression model can accurately predict the prognosis of NSCLC patients. Targeting Nrf2 upregulates the expression of PHKG2 and reverses radiotherapy resistance in NSCLC by promoting iron autophagy and inducing mitochondrial dysfunction, thereby increasing radiotherapy sensitivity.
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BACKGROUND: To investigate the optimal B1,rms value of renal amide proton transfer-weighted (APTw) images and the reproducibility of this value, and to explore the utility of APT imaging of renal masses and kidney tissues. METHODS: APTw images with different B1,rms values were repeatedly recorded in 15 healthy volunteers to determine the optimal value. Two 4-point Likert scales (poor [1] to excellent [4]) were used to evaluate contour clarity and artifacts in masses and normal tissues. The APTw values of masses and normal tissues were then compared in evaluable images (contour clarity score > 1, artifacts score > 1). The APTw of malignant masses, normal tissues, and benign masses were calculated and compared with the Mann-Whitney U test. RESULTS: The optimal scanning parameter of B1,rms was 2 µT, and the APTw images had good agreement in the volunteers. Our study of APTw imaging examined 70 renal masses (13 benign, 57 malignant) and 49 normal kidneys (including those from 15 healthy volunteers). The mean APTw value for renal malignant masses (2.28(1.55)) was different from that for benign masses (0.91(1.30)) (P<0.001), renal cortex (1.30 (1.25)) (P<0.001), renal medulla (1.64 (1.33)) (P<0.05), and renal pelvis (5.49 (2.65)) (P<0.001). CONCLUSION: These preliminary data demonstrate that APTw imaging of the kidneys has potential use as an imaging biomarker for the differentiation of normal tissues, malignant masses, and benign masses.
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Purpose: The objective of this study was to create and validate a novel prediction model that incorporated both multi-modal radiomics features and multi-clinical features, with the aim of accurately identifying acute ischemic stroke (AIS) patients who faced a higher risk of poor outcomes. Methods: A cohort of 461 patients diagnosed with AIS from four centers was divided into a training cohort and a validation cohort. Radiomics features were extracted and selected from diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) images to create a radiomic signature. Prediction models were developed using multi-clinical and selected radiomics features from DWI and ADC. Results: A total of 49 radiomics features were selected from DWI and ADC images by the least absolute shrinkage and selection operator (LASSO). Additionally, 20 variables were collected as multi-clinical features. In terms of predicting poor outcomes in validation set, the area under the curve (AUC) was 0.727 for the DWI radiomics model, 0.821 for the ADC radiomics model, 0.825 for the DWI + ADC radiomics model, and 0.808 for the multi-clinical model. Furthermore, a prediction model was built using all selected features, the AUC for predicting poor outcomes increased to 0.86. Conclusion: Radiomics features extracted from DWI and ADC images can serve as valuable biomarkers for predicting poor clinical outcomes in patients with AIS. Furthermore, when these radiomics features were combined with multi-clinical features, the predictive performance was enhanced. The prediction model has the potential to provide guidance for tailoring rehabilitation therapies based on individual patient risks for poor outcomes.
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OBJECTIVE: Non-small cell lung cancer (NSCLC) often exhibits resistance to radiotherapy, posing significant treatment challenges. This study investigates the role of SMAD3 in NSCLC, focusing on its potential in influencing radiosensitivity via the ITGA6/PI3K/Akt pathway. METHODS: The study utilized gene expression data from the GEO database to identify differentially expressed genes related to radiotherapy resistance in NSCLC. Using the GSE37745 dataset, prognostic genes were identified through Cox regression and survival analysis. Functional roles of target genes were explored using Gene Set Enrichment Analysis (GSEA) and co-expression analyses. Gene promoter methylation levels were assessed using databases like UALCAN, DNMIVD, and UCSC Xena, while the TISCH database provided insights into the correlation between target genes and CAFs. Experiments included RT-qPCR, Western blot, and immunohistochemistry on NSCLC patient samples, in vitro studies on isolated CAFs cells, and in vivo nude mouse tumor models. RESULTS: Fifteen key genes associated with radiotherapy resistance in NSCLC cells were identified. SMAD3 was recognized as an independent prognostic factor for NSCLC, linked to poor patient outcomes. High expression of SMAD3 was correlated with low DNA methylation in its promoter region and was enriched in CAFs. In vitro and in vivo experiments confirmed that SMAD3 promotes radiotherapy resistance by activating the ITGA6/PI3K/Akt signaling pathway. CONCLUSION: High expression of SMAD3 in NSCLC tissues, cells, and CAFs is closely associated with poor prognosis and increased radiotherapy resistance. SMAD3 is likely to enhance radiotherapy resistance in NSCLC cells by activating the ITGA6/PI3K/Akt signaling pathway.
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Fibroblastos Asociados al Cáncer , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Animales , Ratones , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Metilación de ADN/genética , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Tolerancia a Radiación/genética , Regiones Promotoras Genéticas/genética , Perfilación de la Expresión Génica , Línea Celular Tumoral , Proteína smad3/genética , Proteína smad3/metabolismoRESUMEN
Background: Distant metastasis is the leading cause of death in patients with rectal cancer. This study aims to comprehensively analyze the risk factors of distant metastasis in T3 T4 rectal cancer using magnetic resonance imaging (MRI), pathological features, and serum indicators. Methods: The clinicopathological data of 146 cases of T3 T4 rectal cancer after radical resection from January 2015 to March 2023 were retrospectively analyzed. Pre- and postoperative follow-up data of all cases were collected to screen for distant metastatic lesions. Univariate and multivariate Logistic regression methods were used to analyze the relationship between MRI features, pathological results, serum test indexes, and distant metastasis. Results: Of the 146 included patients, synchronous or metachronous distance metastasis was confirmed in 43 (29.4%) cases. The patients' baseline data and univariate analysis showed that mrEMVI, maximum tumor diameter, mr T Stage, pathological N stage, number of lymph node metastasis, cancer nodules, preoperative serum CEA, (Carcinoembryonic antigen) and CA199 were associated with distant metastasis. In the multiple logistic regression model, mrEMVI, pathological N stage, number of lymph node metastasis, maximum tumor diameter, and preoperative serum CEA were identified as independent risk factors for distant metastasis: mrEMVI [odds ratio (OR) = 3.06], pathological N stage (OR = 6.52 for N1 vs N0; OR = 63.47 for N2 vs N0), preoperative serum CEA (OR = 0.27), tumor maximum diameter (OR = 1.03), number of lymph nodes metastasis (OR = 0.62). And, the receiver operating characteristic (ROC) curve was plotted and the area under the curve was calculated (area under the curve [AUC) = 0.817, 95% CI = 0.744-0.890, P < .001]. Conclusions: mrEMVI, pathological N stage, number of lymph node metastasis, maximum tumor diameter and preoperative serum CEA are the independent risk factors for distant metastasis in T3 T4 rectal cancer. A comprehensive analysis of the risk factors for distant metastasis in rectal cancer can provide a reliable basis for formulating individualized treatment strategies, follow-up plans, and evaluating prognosis.
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Polycystic ovary syndrome (PCOS) is a highly heterogeneous and genetically complex endocrine disorder. Although the etiology remains mostly elusive, growing evidence suggests that abnormal changes of DNA methylation correlate well with systemic and tissue-specific dysfunctions in PCOS. Herein, a dehydroepiandrosterone-induced PCOS-like mouse model which has a similar metabolic and reproductive phenotype as human patients with PCOS was generated. It was used to experimentally validate the potential role of aberrant DNA methylation in PCOS in this study. Integrated DNA methylation and transcriptome analysis revealed the potential role of genomic DNA hypomethylation in transcription regulation of PCOS and identified several key candidate genes, including BMP4, Adcy7, Tnfaip3, and Fas, which were regulated by aberrant DNA hypomethylation. Moreover, i.p. injection of S-adenosylmethionine increased the overall DNA methylation level of PCOS-like mice and restored expression of the candidate genes to similar levels as the control, alleviating reproductive and metabolic abnormalities in PCOS-like mice. These findings provide direct evidence showing the importance of normal DNA methylation in epigenetic regulation of PCOS and potential targets for diagnosis and treatment of the disease.
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Metilación de ADN , Síndrome del Ovario Poliquístico , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/patología , Metilación de ADN/genética , Animales , Femenino , Ratones , Modelos Animales de Enfermedad , Transcripción Genética , Epigénesis Genética , Regulación de la Expresión Génica , Humanos , Ratones Endogámicos C57BLRESUMEN
Inorganic metal halide perovskite CsPbX3 (X = I, Br, and Cl) nanocrystals (NCs) are rapidly developed due to their excellent photophysical properties and potential applications in lighting, lasers, and scintillators. However, the materials for growing perovskite NCs are insoluble or hydrolyzed in most green solvents, limiting their further development. Based on rational chemical analysis, an alkali-metal-assisted green-solvent synthesis method for in situ growth of CsPbBr3 NCs within SAPO-34 zeolite with bright luminescence is developed. Water is the only solvent used in the whole process. Surprisingly, by the synergistic effect of the channel structure of SAPO-34 and alkali-metal ions crystallization regulation, the CsPbBr3 NCs embedded in SAPO-34 assisted by Na+ emit bright blue light under ultraviolet illumination, with a 30 nm blue shift comparing to the CsPbBr3 NCs assisted by K+. Moreover, CsPbBr3 NCs can also be grown in mesoporous SiO2 SBA-15 and zeolites including ZSM-5, AlPO-5, and SOD, indicating that the method is universal for in situ growth of luminescent perovskite NCs in porous materials. This alkali-metal-assisted green-solvent synthesis provides a new strategy for developing high-quantum-yield, tunable-emission, and stable perovskite luminescent materials.
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BACKGROUND: Conventional magnetic resonance imaging (MRI) has certain limitations in distinguishing between malignant and benign urinary bladder (UB) lesions. Amide proton transfer (APT) imaging may provide more diagnostic information than diffusion-weighted imaging (DWI) to distinguish between malignant and benign UB. PURPOSE: To investigate the potential of APT imaging in the diagnosis of malignant and benign UB lesions and to compare its diagnostic efficacy with that of conventional DWI. STUDY TYPE: Prospective. SUBJECTS: Eighty patients with UB lesions. FIELD STRENGTH/SEQUENCE: A 3.0 T/turbo spin echo (TSE) T1-weighted and T2-weighted imaging, single-shot echo planar DWI, and three-dimensional TSE APT imaging. ASSESSMENT: Patients underwent radical cystectomy or transurethral resection of the bladder lesions within 2 weeks after CT urography and MRI examination. APT signal intensity in UB lesions was quantified by the asymmetric magnetization transfer ratio (MTRasym). MTRasym and apparent diffusion coefficient (ADC) values were measured and compared between malignant and benign UB lesions. STATISTICAL TESTS: Kolmogorov-Smirnov test, Student's t test or Mann-Whitney U test, Spearman rank correlation coefficient, area under the receiver operating characteristic (ROC) curve (AUC), Delong test, and intraclass correlation coefficient (ICC). The significance threshold was set at P < 0.05. RESULTS: Thirty-two patients had pathologically confirmed benign UB lesions, including 2 bladder leiomyomas, 1 submucosal amyloidosis, 1 inflammatory myofibroblastic tumor, and 28 inflammatory lesions, and 48 patients had pathologically confirmed urothelial carcinoma. Urothelial carcinomas showed significantly higher MTRasym values (1.53% [0.74%] vs. 0.85% [0.23%]) and significantly lower ADC values (1.24 ± 0.34 × 10-3 mm2/s vs. 1.43 ± 0.22 × 10-3 mm2/s) than benign UB lesions. The MTRasym value (AUC = 0.928) was significantly better in differentiating urothelial carcinoma from benign UB lesions than the ADC value (AUC = 0.722). DATA CONCLUSION: APT imaging may have value in discriminating malignant from benign UB lesions and has better diagnostic performance than DWI. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.
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Imagen de Difusión por Resonancia Magnética , Neoplasias de la Vejiga Urinaria , Humanos , Femenino , Masculino , Persona de Mediana Edad , Imagen de Difusión por Resonancia Magnética/métodos , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Anciano , Estudios Prospectivos , Adulto , Vejiga Urinaria/diagnóstico por imagen , Vejiga Urinaria/patología , Anciano de 80 o más Años , Imagen por Resonancia Magnética/métodos , Protones , Diagnóstico Diferencial , Sensibilidad y Especificidad , Amidas , Reproducibilidad de los Resultados , Curva ROCRESUMEN
Histone chaperone FACT (facilitates chromatin transcription) is well known to promote chromatin recovery during transcription. However, the mechanism how FACT regulates genome-wide chromatin accessibility and transcription factor binding has not been fully elucidated. Through loss-of-function studies, we show here that FACT component Ssrp1 is required for DNA replication and DNA damage repair and is also essential for progression of cell phase transition and cell proliferation in mouse embryonic fibroblast cells. On the molecular level, absence of the Ssrp1 leads to increased chromatin accessibility, enhanced CTCF binding, and a remarkable change in dynamic range of gene expression. Our study thus unequivocally uncovers a unique mechanism by which FACT complex regulates transcription by coordinating genome-wide chromatin accessibility and CTCF binding.
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Factor de Unión a CCCTC , Cromatina , Proteínas de Unión al ADN , Regulación de la Expresión Génica , Proteínas del Grupo de Alta Movilidad , Chaperonas de Histonas , Animales , Ratones , Factor de Unión a CCCTC/genética , Factor de Unión a CCCTC/metabolismo , Cromatina/genética , Replicación del ADN , Chaperonas de Histonas/genética , Proteínas de Unión al ADN/genética , Proteínas del Grupo de Alta Movilidad/genética , Células 3T3 NIH , Reparación del ADNRESUMEN
Mild cognitive impairment is considered the prodromal stage of Alzheimer's disease. Accurate diagnosis and the exploration of the pathological mechanism of mild cognitive impairment are extremely valuable for targeted Alzheimer's disease prevention and early intervention. In all, 100 mild cognitive impairment patients and 86 normal controls were recruited in this study. We innovatively constructed the individual morphological brain networks and derived multiple brain connectome features based on 3D-T1 structural magnetic resonance imaging with the Jensen-Shannon divergence similarity estimation method. Our results showed that the most distinguishing morphological brain connectome features in mild cognitive impairment patients were consensus connections and nodal graph metrics, mainly located in the frontal, occipital, limbic lobes, and subcortical gray matter nuclei, corresponding to the default mode network. Topological properties analysis revealed that mild cognitive impairment patients exhibited compensatory changes in the frontal lobe, while abnormal cortical-subcortical circuits associated with cognition were present. Moreover, the combination of multidimensional brain connectome features using multiple kernel-support vector machine achieved the best classification performance in distinguishing mild cognitive impairment patients and normal controls, with an accuracy of 84.21%. Therefore, our findings are of significant importance for developing potential brain imaging biomarkers for early detection of Alzheimer's disease and understanding the neuroimaging mechanisms of the disease.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Conectoma , Humanos , Conectoma/métodos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/patología , Imagen por Resonancia Magnética/métodosRESUMEN
Carbon emission reduction is an essential means to achieve the "double carbon goal," and the scientific and reasonable allocation of carbon emission quotas (CEQ) is the basis for promoting carbon emission reduction. In this study, the first level was based on the entropy TOPSIS scores of provinces under the principles of fairness, efficiency, sustainability, and feasibility and used the K-mean clustering method to cluster the 30 provinces and allocate the CEQ to each zone group; the second level consolidated the impacts of the four principles and the marginal abatement costs of CO2 to allocate CEQ to the provinces within the zone group. Finally, each province's initial spatial balance of CEQ (ISBQ) is classified and evaluated. The study shows that the most quotas are for Guangdong, Zhejiang, and Inner Mongolia, and the least for Ningxia, Shanxi, and Guizhou. This study compares the results of CEQ allocation with the current carbon emission scale and finds that 11 provinces, such as Shandong and Hebei, show a deficit in future carbon emission space, and 19 provinces, such as Hainan and Beijing, show a surplus in carbon emission space. Given each province's different emission reduction tasks and pressures, differentiated emission control policies are the key to achieving China's "2030 target".
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Dióxido de Carbono , Carbono , Carbono/análisis , China , Costos y Análisis de Costo , Dióxido de Carbono/análisis , Desarrollo EconómicoRESUMEN
OBJECTIVE: To investigate the potential of amide proton transfer-weighted (APTw) MRI in identifying benign and malignant renal tumors and to evaluate whether APTw MRI can add diagnostic value to diffusion-weighted imaging (DWI). MATERIALS AND METHODS: Participants with renal tumor underwent preoperative multiparametric MRI, including APTw MRI and DWI. The APTw and apparent diffusion coefficient (ADC) of malignant tumors and benign tumors were calculated independently by two radiologists and compared. The value of the mean APTw and the mean ADC for differentiating malignant and benign tumors was evaluated by receiver operating characteristic analysis. RESULTS: In total, 65 participants (mean age, 59 years ±14; 41 men) were evaluated: 54 with malignant and 11 with benign renal tumors. Malignant renal tumors showed higher mean APTw values [2.03% (1.63) vs 1.00% (1.60); P < 0.01] and lower mean ADC values (1.22 × 10-3 mm2/s ± 0.37 vs 1.51 × 10-3 mm2/s ± 0.37; P < 0.05) than benign renal tumors. The area under the receiver operating characteristic curve (AUC) of APTw, ADC and the combination of them for the identification of benign and malignant renal tumors was 0.78(95% CI: 0.66, 0.87; P < 0.001),0.70(95% CI: 0.54, 0.86; P < 0.05) and 0.79 (95% CI: 0.67, 0.88; P < 0.001). The optimal cutoff value for mean APTw was 2.14% (sensitivity, 74%; specificity, 73%). There was no difference between these three parameters for differentiating malignant from benign renal tumors (P > 0.05). CONCLUSION: The APTw MRI has the potential use as an imaging biomarker for renal malignant and benign tumors.
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Neoplasias Renales , Protones , Masculino , Humanos , Persona de Mediana Edad , Amidas , Imagen de Difusión por Resonancia Magnética/métodos , Imagen por Resonancia Magnética , Neoplasias Renales/diagnóstico por imagen , Diagnóstico Diferencial , Sensibilidad y Especificidad , Estudios RetrospectivosRESUMEN
The application of flue gas desulfurization gypsum (FGDG) improves the soil structure, reduces soil pH, and accelerates soil salt leaching. Biochar amendment to soil can affect the soil infiltration rate, increase soil porosity, decrease soil bulk density, and enhance the water retention capacity. This study investigated the interactive effect of FGDG and biochar on water infiltration characteristics and physicochemical properties as well as determined the optimal amendment rate as a saline-alkaline soil conditioner. Seven experimental schemes were designed, and the newly reclaimed cultivated soil from Pingtan Comprehensive Experimental Zone in Fujian Province, China, was used in an indoor soil column experiment to simulate soil infiltration. Five models were employed to describe the infiltration process. The power function was used to represent the dynamic process of the wetting front. The conclusions of this study are as follows: (1) there was a reduction in the infiltration capacity of saline-alkaline soil (sandy soil) in each treatment, and the application of FGDG alone had the highest inhibition effect compared to the control (CK). The Kostiakov model provides the best fit for the experimental data of soil cumulative infiltration. (2) All treatments increased the total porosity and water content of saline-alkali soil, with the combined application of FGDG and biochar found to be more effective. (3) The application of FGDG alone or in combination with biochar decreased the pH and increased the electrical conductivity of the saline-alkali soil significantly, with the combined application having the most significant effect. In contrast, soil amended with biochar alone had minimal effect on the pH and EC of the soil. (4) The best improvement ratio was achieved with the F1B2 combination (75 g/kg FGDG + 30 g/kg biochar).
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Sulfato de Calcio , Suelo , Sulfato de Calcio/química , Suelo/química , Monitoreo del Ambiente , Carbón Orgánico , Gases , Álcalis , AguaRESUMEN
BACKGROUND: Insulin resistance (IR) in hepatocytes endangers human health, and frequently results in the development of non-alcoholic fatty liver disease (NAFLD). Research on m6A methylation of RNA molecules has gained popularity in recent years; however, the molecular mechanisms regulating the processes of m6A modification and IR are not known. The cytochrome P450 (CYP450) enzyme system, which is mainly found in the liver, is associated with the pathogenesis of NAFLD. However, few studies have been conducted on CYP450 related m6A methylation. Here, we investigated the role of the methyltransferase METTL3 in exacerbating IR in hepatocytes, mainly focusing on the regulation of m6A modifications in CYP2B6. METHODS AND RESULTS: Analysis using dot blot and epitranscriptomic chips revealed that the m6A modification pattern of the transcriptome in high-fat diet (HFD)-induced fatty liver and free fatty acid (FFA)-induced fatty hepatocytes showed significant changes. CYP450 family members, especially Cyp2b10, whose homolog in humans is CYP2B6, led to a noticeable increase in m6A levels in HFD-induced mice livers. Application of the METTL3 methyltransferase inhibitor, STM2457, increased the level of insulin sensitivity in hepatocytes. We then analyzed the role of METTL3 in regulating m6A modification of CYP2B6 in hepatocytes. METTL3 regulated the m6A modification of CYP2B6, and a positive correlation was found between the levels of CYP2B6 translation and m6A modifications. Furthermore, interference with METTL3 expression and exposure to STM2457 inhibited METTL3 activity, which in turn interfered with the phosphorylated insulin receptor substrate (pIRS)-glucose transporter 2 (GLUT2) insulin signaling pathway; overexpression of CYP2B6 hindered IRS phosphorylation and translocation of GLUT2 to membranes, which ultimately exacerbated IR. CONCLUSION: These findings offer unique insights into the role that METTL3-mediated m6A modifications of CYP2B6 play in regulating insulin sensitivity in hepatocytes and provide key information for the development of strategies to induce m6A modifications for the clinical treatment of NAFLD.
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Multidrug resistance (MDR) is one of the major factors causing failure of non-small-cell lung cancer (NSCLC) chemotherapy. Real-time and accurate differentiation between drug-resistant and sensitive NSCLC is of primary importance for guiding the subsequent treatments and improving the therapeutic outcome. However, there is no effective method to provide such an accurate differentiation. This study creates an innovative strategy of integrating H2 O2 -responsive nanoprobes with the quantitative T1 -mapping magnetic resonance imaging (MRI) technique to achieve an accurate differential diagnosis between drug-resistant and sensitive NSCLC in light of differences in H2 O2 content in the tumor microenvironment (TME). The result demonstrates that the synthesized MIL-53(Fe)@MnO2 nanocomposites possess an excellent capability of shortening the cancer longitudinal relaxation time (T1 ) when meeting H2 O2 in TME. T1 -mapping MRI could sensitively detect this T1 variation (about 2.6-fold that of T1-weighted imaging (T1 WI)) to accurately differentiate the H2 O2 content between drug-resistant and sensitive NSCLC. In addition, the quantitative data provided by the T1 -mapping MRI dedicates correct comparison across imaging tests and is more reliable than T1 WI, thus giving it a chance for precise assessment of the anti-cancer effect. This innovative strategy of merging TME adaptable nanoprobes with the quantitative MRI technique provides a new approach for the precise diagnosis of multidrug-resistant NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/patología , Medios de Contraste , Compuestos de Manganeso , Diagnóstico Diferencial , Óxidos , Imagen por Resonancia Magnética/métodos , Microambiente TumoralRESUMEN
Understanding and controlling crystallization is crucial for high-quality perovskite films and efficient solar cells. Herein, the issue of defects in formamidinium lead iodide (FAPbI3 ) formation is addressed, focusing on the role of intermediates. A comprehensive picture of structural and carrier evolution during crystallization is demonstrated using in situ grazing-incidence wide-angle X-ray scattering, ultraviolet-visible spectroscopy and photoluminescence spectroscopy. Three crystallization stages are identified: precursors to the δ-FAPbI3 intermediate, then to α-FAPbI3 , where defects spontaneously emerge. A hydrogen-sulfate-based ionic liquid additive is found to enable the phase-conversion pathway of precursors â solvated intermediates â α-FAPbI3 , during which the spontaneous generation of δ-FAPbI3 can be effectively circumvented. This additive extends the initial growth kinetics and facilitates solvent-FA+ ion exchange, which results in the self-elimination of defects during crystallization. Therefore, the improved crystallization dynamics lead to larger grain sizes and fewer defects within thin films. Ultimately, the improved perovskite crystallization dynamics enable high-performance solar cells, achieving impressive efficiencies of 25.14% at 300 K and 26.12% at 240 K. This breakthrough might open up a new era of application for the emerging perovskite photovoltaic technology to low-temperature environments such as near-space and polar regions.
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RATIONALE AND OBJECTIVES: This study was designed to investigate the association between the perivascular fat attenuation index (FAI) and atherosclerotic plaque formation proximal to myocardial bridging (MB) of the left anterior descending artery (LAD) within 3 years. MATERIALS AND METHODS: LAD-MB patients who underwent coronary computed tomography angiography at least twice between January 2016 and December 2022 were retrospectively included in this study. In total, 99 LAD-MB patients were included in the study. Based on the formation of atherosclerotic plaques proximal to LAD-MB during follow-up, the patients were classified into two groups: LAD-MB with plaque formation and LAD-MB without plaque formation within 3 years. The anatomical features, clinical factors, and proximal perivascular FAI of LAD-MB were measured and recorded. The association of the previously mentioned factors with the presence of atherosclerotic plaque proximal to LAD-MB was determined. RESULTS: The results showed that MB length, MB stenosis, and the perivascular FAI were significant predictors of the formation of atherosclerotic plaques proximal to LAD-MB. The area under the curve of the combined predictive model incorporating MB length, MB stenosis, and the perivascular FAI was 0.901(95% confidence interval: 0.824-0.952), with higher diagnostic performance than any other single parameter (all P < 0.05). Moreover, dynamic changes in the perivascular FAI of the vascular segments proximal to LAD-MB were higher in high-risk plaques than in non-high-risk plaques (P = 0.003). CONCLUSION: The combined use of the perivascular FAI, MB length, and MB stenosis may enable prediction of the probability of atherosclerotic plaque formation proximal to LAD-MB within 3 years. Dynamic changes in perivascular FAI were associated with the vulnerability of plaques proximal to LAD-MB.
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Enfermedad de la Arteria Coronaria , Puente Miocárdico , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico , Puente Miocárdico/complicaciones , Angiografía Coronaria/métodos , Constricción Patológica/complicaciones , Estudios Retrospectivos , Vasos Coronarios/diagnóstico por imagen , Tejido Adiposo/diagnóstico por imagenRESUMEN
BACKGROUND: In order to identify individuals with chronic internal carotid artery occlusion (CICAO), it is essential to understand the integrity of the circle of Willis (CoW). This understanding is important as it may determine the potential benefits of active medical and endovascular treatments. PURPOSE: The objective of this study is to assess whether diminished integrity of the CoW can serve as a useful marker for identifying individuals with more severe impairment in cerebral blood perfusion and a higher incidence of cerebral infarction among asymptomatic or mildly affected patients with CICAO. MATERIALS AND METHODS: We conducted a retrospective review of asymptomatic or mildly affected patients with newly diagnosed CICAO who did not receive reperfusion therapies. The categorization of patients into good or poor integrity groups was based on the assessment of CoW integrity using CTA. We evaluated the volume and value of prolonged time to peak (TTP) in both groups, as well as the occurrence of new cerebral infarctions. Our analysis involved multivariate regression and receiver operating characteristic (ROC) analysis. RESULTS: Hemodynamic abnormalities characterized by prolonged TTP were observed in the affected side's blood supply region in all 38 patients. There was a notable difference in the volume and value of prolonged TTP between the two groups (P < 0.001). Correlation analyses based on CTP and CTA parameters revealed a negative relationship between CoW scores and both the abnormal volume (r = -0.624, P = 0.000) and value (r = -0.589, P = 0.000) of prolonged TTP. Upon multivariable adjustment, the independent predictors for new cerebral infarction and higher volume of prolonged TTP were solely the CoW status, with respective estimates of (b = 6.05; 95% confidence interval [CI]: 1.619, 22.619; P = 0.007) and (b = 35.486; 95% CI: 4.697, 268.088; P = 0.001). CONCLUSION: Assessing the integrity of the CoW is crucial in evaluating abnormal perfusion in asymptomatic or mildly affected individuals who are newly diagnosed with CICAO and have not undergone reperfusion therapy.
Asunto(s)
Enfermedades de las Arterias Carótidas , Estenosis Carotídea , Trombosis , Humanos , Círculo Arterial Cerebral/diagnóstico por imagen , Arteria Carótida Interna/diagnóstico por imagen , Estenosis Carotídea/diagnóstico por imagen , Infarto Cerebral , Circulación CerebrovascularRESUMEN
Metal-halide perovskites possess great potential for electrochemical water splitting that has not been realized due to their intolerance to water. Here, methylammonium lead halide perovskites (MAPbX3 ) are used to electrocatalyze water oxidation in aqueous electrolytes by creating MAPbX3 @AlPO-5 host-guest composites. Due to the protective feature of the zeolite matrix, halide perovskite nanocrystals (NCs) confined in aluminophosphate AlPO-5 zeolites achieve an excellent stability in water. The resultant electrocatalyst undergoes dynamic surface restructuring during the oxygen evolution reaction (OER) with the formation of an edge-sharing α-PbO2 active layer. The existence of charge-transfer interactions at the MAPbX3 /α-PbO2 interface significantly modulates the surface electron density of the α-PbO2 and optimizes the adsorption free energy of oxygen-containing intermediate species. Furthermore, the soft-lattice nature of halide perovskites enables more facile triggering of lattice-oxygen oxidation of nanostructured α-PbO2 , exhibiting pH-dependent OER activity and non-concerted proton-electron transfer for MAPbX3 @AlPO-5 composite. As a result, the developed MAPbBr3 @AlPO-5 composite manifests an ultralow overpotential of 233 mV at 10 mA cm-2 in 1 m KOH. These findings offer facile access to halide perovskite applied to water electrolysis with enhanced intrinsic activity, providing a new paradigm for designing high-efficiency OER electrocatalysts.
RESUMEN
Accurately evaluating tumor responses to immunotherapy is clinically relevant. However, non-invasive, real-time visualization techniques to evaluate tumor immunotherapy are still lacking. Herein, a smart responsive fluorescence-MR dual-modal nanoprobe, QM(GP)-MZF(CP), is reported that can be targeted for cleavage by the cytotoxic T cell activation marker granzyme B and the apoptosis-related marker cysteine-aspartic acid-specific protease 3 (Caspase-3). The probe uses quinoline-malononitrile (QM), an aggregation-induced emission luminogen, and Mn-Zn ferrite magnetic nanoparticles (MZF-MNPs), a T2-weighted imaging (T2WI) contrast agent, as imaging molecules that are linked with the substrate peptides specific to granzyme B and Caspase-3. Therefore, both granzyme B and Caspase-3 can target and cleave the substrate peptides in QM(GP)-MZF(CP). Via aggregation-induced fluorescence imaging of QM and the aggregation-induced T2WI-enhanced imaging effect of MZF-MNPs, the status of T cells after tumor immunotherapy and the subsequent triggering of tumor cell apoptosis can be determined to identify tumor responsiveness to immunotherapy and thereby evaluate the effectiveness of this therapy in the early stages of treatment.