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BACKGROUND: According to clinical practice guidelines, transarterial chemoembolization (TACE) is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma (HCC). Early prediction of treatment response can help patients choose a reasonable treatment plan. This study aimed to investigate the value of the radiomic-clinical model in predicting the efficacy of the first TACE treatment for HCC to prolong patient survival. METHODS: A total of 164 patients with HCC who underwent the first TACE from January 2017 to September 2021 were analyzed. The tumor response was assessed by modified response evaluation criteria in solid tumors (mRECIST), and the response of the first TACE to each session and its correlation with overall survival were evaluated. The radiomic signatures associated with the treatment response were identified by the least absolute shrinkage and selection operator (LASSO), and four machine learning models were built with different types of regions of interest (ROIs) (tumor and corresponding tissues) and the model with the best performance was selected. The predictive performance was assessed with receiver operating characteristic (ROC) curves and calibration curves. RESULTS: Of all the models, the random forest (RF) model with peritumor (+10 mm) radiomic signatures had the best performance [area under ROC curve (AUC) = 0.964 in the training cohort, AUC = 0.949 in the validation cohort]. The RF model was used to calculate the radiomic score (Rad-score), and the optimal cutoff value (0.34) was calculated according to the Youden's index. Patients were then divided into a high-risk group (Rad-score > 0.34) and a low-risk group (Rad-score ≤ 0.34), and a nomogram model was successfully established to predict treatment response. The predicted treatment response also allowed for significant discrimination of Kaplan-Meier curves. Multivariate Cox regression identified six independent prognostic factors for overall survival, including male [hazard ratio (HR) = 0.500, 95% confidence interval (CI): 0.260-0.962, P = 0.038], alpha-fetoprotein (HR = 1.003, 95% CI: 1.002-1.004, P < 0.001), alanine aminotransferase (HR = 1.003, 95% CI: 1.001-1.005, P = 0.025), performance status (HR = 2.400, 95% CI: 1.200-4.800, P = 0.013), the number of TACE sessions (HR = 0.870, 95% CI: 0.780-0.970, P = 0.012) and Rad-score (HR = 3.480, 95% CI: 1.416-8.552, P = 0.007). CONCLUSIONS: The radiomic signatures and clinical factors can be well-used to predict the response of HCC patients to the first TACE and may help identify the patients most likely to benefit from TACE.
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PURPOSE: Bladder cancer is a common malignant tumor of the urinary system, with the fourth-highest incidence of male malignant tumors in Europe and the United States. So far, the mechanism of bladder cancer progression and metastasis has not been clarified. The aim of our study was to validate the way of long noncoding RNA (lncRNA) KCNMB2-AS1 on the metabolism and growth of bladder cancer cells by miR-3194-3p/SMAD5. PATIENTS AND METHODS: The Gene Expression was analyzed by qRT-PCR in bladder cancer tissues and cell lines, with the highly expressed KCNMB2-AS1 screened out. Cell proliferation was detected by Edu staining and clone formation assay, cell migration, and invasion by wound healing and transwell assays. Cell stemness was determined by assessing sphere-forming ability and stemness marker. Correlation between miRNA and lncRNA/gene was verified by dual-luciferase assay and RIP, and the effect of KCNMB2-AS1 on bladder cancer growth by nude mice tumor formation experiment. RESULTS: Here, we revealed the increased level of KCNMB2-AS1 in bladder cancer for the first time. Knockdown of KCNMB2-AS1 in vitro prevented the ability of proliferation, metastasis, and stemness of cancer cells. In vivo, the silencing of KCNMB2-AS1 also prevented tumor growth in vivo. Next, we revealed that KCNMB2-AS1 could interact with miR-3194-3p and uncovered that SAMD5 was a downstream target of miR-3194-3p. CONCLUSION: In conclusion, KCNMB2-AS1 mediated the bladder cancer cells progress by regulating the miR-3194-3p/SAMD5 signal pathway, which would provide a new target for bladder cancer research.
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Junenol based-eudesmanolides have been detected in many compositae plant species and were reported to exhibit various pharmacological activities. So far, the gene encoding junenol synthase has never been isolated. Here we report the molecular cloning and functional analysis of a 10-epi-junenol synthase from Inula hupehensis (designated IhsTPS1). IhsTPS1 converts the substrate farnesyl diphosphate into multiple sesquiterpenes with the product 10-epi-junenol being predominant. The transcript levels of IhsTPS1 correlate well with the accumulation pattern of 10-epi-junenol in I. hupehensis organs, supporting its biochemical roles in vivo.
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Transferasas Alquil y Aril/genética , Inula/enzimología , Inula/genética , Proteínas de Plantas/genética , Transferasas Alquil y Aril/metabolismo , Vías Biosintéticas/genética , Clonación Molecular , ADN Complementario/genética , Cromatografía de Gases y Espectrometría de Masas , Regulación Enzimológica de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Filogenia , Proteínas de Plantas/metabolismo , Fosfatos de Poliisoprenilo/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Sesquiterpenos/química , Sesquiterpenos/metabolismoRESUMEN
As part of the efforts to understand isoflavonoid metabolism in Pueraria lobata at the molecular level, the cDNAs encoding two divergent 4-coumarateâ :â coenzyme A ligases (4CLs, designated Pl4CL1 and Pl4CL2, respectively) were isolated from P. lobata roots. Sequence analysis revealed that Pl4CL1 had an N-terminal extension of twenty-one amino acid residues compared to Pl4CL2. Phylogenetic analysis showed that Pl4CL1 and Pl4CL2 fell into angiosperm Class II and Class I, respectively. Through in vitro biochemical assays, both Pl4CLs were found to have the capacity to utilize 4-coumarate and trans-cinnamate as substrates, while neither of them could convert sinapate. Pl4CL2 had a broader substrate specificity than Pl4CL1. The affinity of Pl4CL1 for 4-coumarate was 2.6-fold higher than that of Pl4CL2 (with the Km values of 3.5 µM and 9.1 µM, respectively). Combining the dataset including gene expression profiles, metabolites measurements, and biochemical properties, our results indicated that Pl4CL1, just as other angiosperm Class II 4CLs, might play a role in isoflavone biosynthesis in P. lobata, while Pl4CL2 belongs to angiosperm Class I, and may function as a housekeeping enzyme concerning lignification.
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Aminoácidos/análisis , Cinamatos/metabolismo , Coenzima A Ligasas , Ácidos Cumáricos/metabolismo , Isoflavonas/biosíntesis , Lignanos/biosíntesis , Pueraria , Secuencia de Aminoácidos , Clonación Molecular , Coenzima A Ligasas/química , Coenzima A Ligasas/genética , Coenzima A Ligasas/metabolismo , ADN Complementario , Datos de Secuencia Molecular , Filogenia , Raíces de Plantas/enzimología , Raíces de Plantas/metabolismo , Pueraria/enzimología , Pueraria/genética , Pueraria/metabolismo , Especificidad por SustratoRESUMEN
Tb(3+)-doped CePO4 flower-like clusters were hydrothermally synthesized without using any template or surfactant by varying the reactant Tb3+ cation concentration. It was observed that the flower-like clusters were composed by nanowires with a diameter of about 80-90 nm and lengths up to 1 microm. The structures, morphologies, sizes and luminescence properties of the products were studied by X-ray powder diffraction (XRD), field-emission scanning electronic microscopy (FE-SEM), and luminescence spectra. With the reactant Ce3+ /Tb3+ molar ratio of 0.850 : 0.150, the uniform flower-like clusters were actually composed of a self-assembly of the oriented nanowires through an Tb(3+)-induced in the excessive PO4(3-). It was found that the reactant Ce3+/Tb3+ molar ratio and phosphoric acid played key roles in the morphology control of the product. A possible formation mechanism for the flower-like morphology was also proposed. The luminescence properties of CePO4 : Tb flower-like cluster were performed, indicating that the strongest emission intensity was reached with 0.850 : 0.150 molar ratios of Ce3+/Tb3+.