RESUMEN
Background: This study aimed to establish a novel quantification system of ferroptosis patterns and comprehensively analyze the relationship between ferroptosis score (FS) and the immune cell infiltration (ICI) characterization, tumor mutation burden (TMB), prognosis, and therapeutic sensitivity in left-sided and right-sided colon cancers (LCCs and RCCs, respectively). Methods: We comprehensively evaluated the ferroptosis patterns in 444 LCCs and RCCs based on 59 ferroptosis-related genes (FRGs). The FS was constructed to quantify ferroptosis patterns by using principal component analysis algorithms. Next, the prognostic value and therapeutic sensitivities were evaluated using multiple methods. Finally, we performed weighted gene co-expression network analysis (WGCNA) to identify the key FRGs. The IMvigor210 cohort, TCGA-COAD proteomics cohort, and Immunophenoscores were used to verify the predictive abilities of FS and the key FRGs. Results: Two ferroptosis clusters were determined. Ferroptosis cluster B demonstrated a high degree of congenital ICI and stromal-related signal enrichment with a poor prognosis. The prognosis, response of targeted inhibitors, and immunotherapy were significantly different between high and low FS groups (HSG and LSG, respectively). HSG was characterized by high TMB and microsatellite instability-high subtype with poor prognosis. Meanwhile, LSG was more likely to benefit from immunotherapy. ALOX5 was identified as a key FRG based on FS. Patients with high protein levels of ALOX5 had poorer prognoses. Conclusion: This work revealed that the evaluation of ferroptosis subtypes will contribute to gaining insight into the heterogeneity in LCCs and RCCs. The quantification for ferroptosis patterns played a non-negligible role in predicting ICI characterization, prognosis, and individualized immunotherapy strategies.
Asunto(s)
Neoplasias del Colon , Ferroptosis , Biomarcadores de Tumor/genética , Neoplasias del Colon/genética , Neoplasias del Colon/terapia , Ferroptosis/genética , Humanos , Inmunoterapia , PronósticoRESUMEN
Unlike general ventilation, personalized ventilation can improve thermal comfort and conserve energy based on individual differences. It can also provide every individual the ability to control fresh air exposure and ensure good indoor air quality. However, determining how to improve air supply efficiency while avoiding a draft sensation is still a difficult question. This paper introduces a body movement-based personalized targeted air supply device. Two indices, size target value Ts and velocity target value Tr , are introduced to evaluate the degree to which the created flow field reaches the desired level. Additionally, the air supply effect of the device is compared with that of other devices. This research shows that the personalized targeted air supply device can successfully deliver air to the target area and improve air supply accessibility in the target area. The multinozzle coupling air supply mode produces a flow field air velocity of approximately 0.3 m/s, thus effectively avoiding a draft sensation. Compared with that of other personalized nozzles, the energy consumption is reduced significantly, by 88.2%, while the air supply accessibility can be increased by 48% with equivalent energy consumption.
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Contaminación del Aire Interior/estadística & datos numéricos , Ventilación/métodos , Aire Acondicionado , Movimientos del Aire , Humanos , Movimiento , TemperaturaRESUMEN
Non-small cell lung cancer (NSCLC) is an aggressive malignancy with increasing worldwide incidence and is characterized by dismal prognosis due to its early recurrence and metastasis. Accumulating evidence documented that aberrantly expressed circular RNAs (circRNAs) are critically involved in tumorigenesis. In the current study, we focused on a novel circRNA, circ_0016760 in NSCLC. qRT-PCR was carried out to determine the expression level of circ_0016760 in tissue samples and cell lines. The clinical value of circ_0016760 was also investigated. The functions of circ_0016760 was explored by CCK-8, colony formation, flow cytometry, Transwell and animal experiments. Luciferase reporter assays were conducted to investigate the association between circ_0016760 and miR-1287 and miR-1287 and GAGE1. We found that circ_0016760 was enhanced in NSCLC tissues and cells and the upregulation of circ_0016760 is associated with advanced TNM stages, lymph node metastasis and adverse prognosis in NSCLC patients. Moreover, circ_0016760 could significantly promote cell growth and metastatic properties and inhibit cell apoptosis in NSCLC cells. In mechanism, circ_0016760 functioned as a sponge for miR-1287 and regulated the expression of GAGE1. Subsequently, functional assays illustrated that the oncogenic properties of circ_0016760 is partly attribute to the regulation of miR-1287/GAGE1 axis. In summary, circ_0016760/miR-1287/GAGE1 signaling might play vital roles in the tumorigenesis and progression of NSCLC.
Asunto(s)
Antígenos de Neoplasias/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , MicroARNs/metabolismo , Proteínas de Neoplasias/metabolismo , ARN/metabolismo , Regulación hacia Arriba , Animales , Antígenos de Neoplasias/genética , Apoptosis , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Línea Celular , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Neoplasias Experimentales/diagnóstico , Neoplasias Experimentales/metabolismo , Pronóstico , ARN/genética , ARN CircularRESUMEN
We aimed to investigate the effects of miR-200c binding to fibronectin 1 (FN1) on proliferation, migration and invasion of gastric cancer (GC) cells. A total of 52 GC tissues and their corresponding normal adjacent tissue samples were collected. Then, miR-200c and FN1 were tested using quantitative real-time RT-PCR in the clinical specimens and GC cells, while immunohistochemistry and western blotting assay were carried out to detect FN1 expressions. Dual luciferase reporter gene assay was used to assess the effect of miR-200c on the luciferase activity of FN1 3'UTR. BGC-823 cells were transfected with miR-200c mimics, miR-200c inhibitors and FN1 siRNA, respectively. The effects of miR-200c inhibitors and FN1 siRNA on cellular proliferation, migration and invasion were detected through MTT assay and Transwell assay. Compared to normal tissues and cells, miR-200c was significantly down-regulated and FN1 was significantly up-regulated (P<0.01). Dual luciferase reporter gene assay showed that miR-200c could specifically bind to the 3'-UTR of FN1 and significantly repress the luciferase activity (P<0.01). Both mRNA and protein expressions of FN1 were decreased significantly in GC cells when miR-200c was over expressed. The proliferation, migration and invasion of GC cells could be suppressed by over-expression of miR-200c or down-regulation of FN1. In conclusion, miR-200c was significantly down-regulated in both GC tissues and cell lines, while FN1 presented the opposite trends. Besides, miR-200c inhibited the proliferation, migration and invasion of GC cells through binding to FN1.