7 research outputs found

    From Decolonial to the Postcolonial: Trauma of an Unfinished Agenda

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    Expression stability of the candidate reference genes under different conditions. (DOCX 13 kb

    DataSheet_1_PI3K/AKT/mTOR pathway-derived risk score exhibits correlation with immune infiltration in uveal melanoma patients.zip

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    Uveal melanoma (UVM) is a rare but highly aggressive intraocular tumor with a poor prognosis and limited therapeutic options. Recent studies have implicated the PI3K/AKT/mTOR pathway in the pathogenesis and progression of UVM. Here, we aimed to explore the potential mechanism of PI3K/AKT/mTOR pathway-related genes (PRGs) in UVM and develop a novel prognostic-related risk model. Using unsupervised clustering on 14 PRGs profiles, we identified three distinct subtypes with varying immune characteristics. Subtype A demonstrated the worst overall survival and showed higher expression of human leukocyte antigen, immune checkpoints, and immune cell infiltration. Further enrichment analysis revealed that subtype A mainly functioned in inflammatory response, apoptosis, angiogenesis, and the PI3K/AKT/mTOR signaling pathway. Differential analysis between different subtypes identified 56 differentially expressed genes (DEGs), with the major enrichment pathway of these DEGs associated with PI3K/AKT/mTOR. Based on these DEGs, we developed a consensus machine learning-derived signature (RSF model) that exhibited the best power for predicting prognosis among 76 algorithm combinations. The novel signature demonstrated excellent robustness and predictive ability for the overall survival of patients. Moreover, we observed that patients classified by risk scores had distinguishable immune status and mutation. In conclusion, our study identified a consensus machine learning-derived signature as a potential biomarker for prognostic prediction in UVM patients. Our findings suggest that this signature is correlated with tumor immune infiltration and may serve as a valuable tool for personalized therapy in the clinical setting.</p

    Table_1_PI3K/AKT/mTOR pathway-derived risk score exhibits correlation with immune infiltration in uveal melanoma patients.docx

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    Uveal melanoma (UVM) is a rare but highly aggressive intraocular tumor with a poor prognosis and limited therapeutic options. Recent studies have implicated the PI3K/AKT/mTOR pathway in the pathogenesis and progression of UVM. Here, we aimed to explore the potential mechanism of PI3K/AKT/mTOR pathway-related genes (PRGs) in UVM and develop a novel prognostic-related risk model. Using unsupervised clustering on 14 PRGs profiles, we identified three distinct subtypes with varying immune characteristics. Subtype A demonstrated the worst overall survival and showed higher expression of human leukocyte antigen, immune checkpoints, and immune cell infiltration. Further enrichment analysis revealed that subtype A mainly functioned in inflammatory response, apoptosis, angiogenesis, and the PI3K/AKT/mTOR signaling pathway. Differential analysis between different subtypes identified 56 differentially expressed genes (DEGs), with the major enrichment pathway of these DEGs associated with PI3K/AKT/mTOR. Based on these DEGs, we developed a consensus machine learning-derived signature (RSF model) that exhibited the best power for predicting prognosis among 76 algorithm combinations. The novel signature demonstrated excellent robustness and predictive ability for the overall survival of patients. Moreover, we observed that patients classified by risk scores had distinguishable immune status and mutation. In conclusion, our study identified a consensus machine learning-derived signature as a potential biomarker for prognostic prediction in UVM patients. Our findings suggest that this signature is correlated with tumor immune infiltration and may serve as a valuable tool for personalized therapy in the clinical setting.</p

    Table_2_PI3K/AKT/mTOR pathway-derived risk score exhibits correlation with immune infiltration in uveal melanoma patients.docx

    No full text
    Uveal melanoma (UVM) is a rare but highly aggressive intraocular tumor with a poor prognosis and limited therapeutic options. Recent studies have implicated the PI3K/AKT/mTOR pathway in the pathogenesis and progression of UVM. Here, we aimed to explore the potential mechanism of PI3K/AKT/mTOR pathway-related genes (PRGs) in UVM and develop a novel prognostic-related risk model. Using unsupervised clustering on 14 PRGs profiles, we identified three distinct subtypes with varying immune characteristics. Subtype A demonstrated the worst overall survival and showed higher expression of human leukocyte antigen, immune checkpoints, and immune cell infiltration. Further enrichment analysis revealed that subtype A mainly functioned in inflammatory response, apoptosis, angiogenesis, and the PI3K/AKT/mTOR signaling pathway. Differential analysis between different subtypes identified 56 differentially expressed genes (DEGs), with the major enrichment pathway of these DEGs associated with PI3K/AKT/mTOR. Based on these DEGs, we developed a consensus machine learning-derived signature (RSF model) that exhibited the best power for predicting prognosis among 76 algorithm combinations. The novel signature demonstrated excellent robustness and predictive ability for the overall survival of patients. Moreover, we observed that patients classified by risk scores had distinguishable immune status and mutation. In conclusion, our study identified a consensus machine learning-derived signature as a potential biomarker for prognostic prediction in UVM patients. Our findings suggest that this signature is correlated with tumor immune infiltration and may serve as a valuable tool for personalized therapy in the clinical setting.</p

    DataSheet1.XLSX

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    <p>Uridine diphosphate (UDP)-glycosyltransferases (UGTs) are major phase II enzymes that conjugate a variety of small lipophilic molecules with UDP sugars and alter them into more water-soluble metabolites. Therefore, glucosidation plays a major role in the inactivation and excretion of a great variety of both endogenous and exogenous compounds. In this study, two inhibitors of UGT enzymes, sulfinpyrazone and 5-nitrouracil, significantly increased the toxicity of thiamethoxam against the resistant strain of Aphis gossypii, which indicates that UGTs are involved in thiamethoxam resistance in the cotton aphid. Based on transcriptome data, 31 A. gossypii UGTs belonging to 11 families (UGT329, UGT330, UGT341, UGT342, UGT343, UGT344, UGT345, UGT348, UGT349, UGT350, and UGT351) were identified. Compared with the thiamethoxam-susceptible strain, the transcripts of 23 UGTs were elevated, and the transcripts of 13 UGTs (UGT344J2, UGT348A2, UGT344D4, UGT341A4, UGT343B2, UGT342B2, UGT350C3, UGT344N2, UGT344A14, UGT344B4, UGT351A4, UGT344A11, and UGT349A2) were increased by approximately 2.0-fold in the resistant cotton aphid. The suppression of selected UGTs significantly increased the insensitivity of resistant aphids to thiamethoxam, suggesting that the up-regulated UGTs might be associated with thiamethoxam tolerance. This study provides an overall view of the possible metabolic factor UGTs that are relevant to the development of insecticide resistance. The results might facilitate further work to validate the roles of these UGTs in thiamethoxam resistance.</p

    <i>CF</i><sub><i>2</i></sub><i>–II</i> Alternative Splicing Isoform Regulates the Expression of Xenobiotic Tolerance-Related Cytochrome P450 <i>CYP6CY22</i> in <i>Aphis gossypii</i> Glover

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    The expression of P450 genes is regulated by trans-regulatory factors or cis-regulatory elements and influences how endogenous or xenobiotic substances are metabolized in an organism’s tissues. In this study, we showed that overexpression of the cytochrome P450 gene, CYP6CY22, led to resistance to cyantraniliprole in Aphis gossypii. The expression of CYP6CY22 increased in the midgut and remaining carcass of the CyR strain, and after repressing the expression of CYP6CY22, the mortality of cotton aphids increased 2.08-fold after exposure to cyantraniliprole. Drosophila ectopically expressing CYP6CY22 exhibited tolerance to cyantraniliprole and cross-tolerance to xanthotoxin, quercetin, 2-tridecanone, tannic acid, and nicotine. Moreover, transcription factor CF2–II (XM_027994540.2) is transcribed only as the splicing variant isoform CF2–II-AS, which was found to be 504 nucleotides shorter than CF2–II in A. gossypii. RNAi and yeast one-hybrid (Y1H) results indicated that CF2–II-AS positively regulates CYP6CY22 and binds to cis-acting element p (−851/-842) of CYP6CY22 to regulate its overexpression. The above results indicated that CYP6CY22 was regulated by the splicing isoform CF2-II-AS, which will help us further understand the mechanism of transcriptional adaption of cross-tolerance between synthetic insecticides and plant secondary metabolites mediated by P450s
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