RESUMO
PURPOSE: The rising global high incidence of differentiated thyroid carcinoma (DTC) has led to a significant increase in patients presenting with lung metastasis of DTC (LMDTC). This population poses a significant challenge in clinical practice, necessitating the urgent development of effective risk stratification methods and predictive tools for lung metastasis. EXPERIMENTAL DESIGN: Through proteomic analysis of large samples of primary lesion and dual validation employing parallel reaction monitoring and IHC, we identified eight hub proteins as potential biomarkers. By expanding the sample size and conducting statistical analysis on clinical features and hub protein expression, we constructed three risk prediction models. RESULTS: This study identified eight hub proteins-SUCLG1/2, DLAT, IDH3B, ACSF2, ACO2, CYCS, and VDAC2-as potential biomarkers for predicting LMDTC risk. We developed and internally validated three risk prediction models incorporating both clinical characteristics and hub protein expression. Our findings demonstrated that the combined prediction model exhibited optimal predictive performance, with the highest discrimination (AUC: 0.986) and calibration (Brier score: 0.043). Application of the combined prediction model within a specific risk threshold (0-0.97) yielded maximal clinical benefit. Finally, we constructed a nomogram based on the combined prediction model. CONCLUSIONS: As a large sample size study in LMDTC research, the identification of biomarkers through primary lesion proteomics and the development of risk prediction models integrating clinical features and hub protein biomarkers offer valuable insights for predicting LMDTC and establishing personalized treatment strategies.
Assuntos
Biomarcadores Tumorais , Neoplasias Pulmonares , Nomogramas , Proteômica , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico , Biomarcadores Tumorais/metabolismo , Proteômica/métodos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Medição de Risco/métodos , Prognóstico , Adulto , IdosoRESUMO
Invariant NK T (iNKT) cells are innate-like lymphocytes that can recognize the lipid Ag presented by MHC I like molecule CD1d. Distinct tissue distribution of iNKT cells subsets implies a contribution of these subsets to their related tissue regional immunity. iNKT cells are enriched in liver, an organ with unique immunological properties. Whether liver-specific iNKT cells exist and dedicate to the liver immunity remains elusive. Here, a liver-specific CD24+ iNKT subset is shown. Hepatic CD24+ iNKT cells show higher levels of proliferation, glucose metabolism, and mTOR activity comparing to CD24- iNKT cells. Although CD24+ iNKT cells and CD24- iNKT cells in the liver produce similar amounts of cytokines, the hepatic CD24+ iNKT cells exhibit lower granzyme B production. These liver-specific CD24+ iNKT cells are derived from thymus and differentiate into CD24+ iNKT in the liver microenvironment. Moreover, liver microenvironment induces the formation of CD24+ conventional T cells as well, and these cells exhibit higher proliferation ability but lower granzyme B production in comparison with CD24- T cells. The results propose that liver microenvironment might induce the generation of liver-specific iNKT subset that might play an important role in maintaining liver homeostasis.
Assuntos
Células T Matadoras Naturais , Antígenos CD1d/metabolismo , Citocinas/metabolismo , Granzimas/metabolismo , Fígado , Ativação Linfocitária , Subpopulações de Linfócitos TRESUMO
Invariant NKT (iNKT) cells have been shown to help B cells in a cognate or noncognate manner; however, whether cognate iNKT cell help induces B cell memory responses remains controversial, and the underlying mechanisms are still unclear. In this study, we demonstrated that, in the absence of follicular helper T cells, cognate iNKT cell help could promote B cell memory responses in mice that were dependent on the formation of memory follicular helper iNKT (iNKTFH) cells and their interactions with memory B cells in recall responses. Generation of memory iNKTFH cells required lipid Ag presentation by dendritic cells but not by B cells. Upon rechallenge, memory iNKTFH cells recognized lipid Ags presented by memory B cells, which recalled iNKTFH effector cells and elicited B cell memory responses. However, LPS, which promoted the synthesis of self-lipids, failed to elicit recall responses in the absence of exogenous lipid Ags.
Assuntos
Formação de Anticorpos/imunologia , Linfócitos B/imunologia , Memória Imunológica/imunologia , Células T Matadoras Naturais/imunologia , Animais , Lipídeos/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The effects of pyrite and bornite on bioleaching of two different chalcopyrite samples by Leptospirillum ferriphilum were studied for the first time. Results showed that bioleaching behaviors of the two chalcopyrite samples were extremely different. Bornite decreased the redox potential (ORP) and maintained it at an appropriate range (380-480 mV vs. Ag/AgCl) to promote chalcopyrite (A) dissolution, but caused the redox potential out of the optimum range and inhibited chalcopyrite (B) dissolution. Large amount of pyrite decreased the redox potential and maintained it at an optimum range to promote chalcopyrite (A) dissolution, while increased the redox potential and kept it at appropriate range for a longer period of time to enhance the dissolution rate of chalcopyrite (B). Chalcopyrite (B) had significantly higher values of conductivity and oxidation-reduction rate when compared with those of chalcopyrite (A). The work is potentially useful in interpreting the inconsistence of the researches of chalcopyrite hydrometallurgy.