Profiling of deubiquitinases that control virulence in the pathogenic plant fungus Fusarium graminearum.

Eukaryotes have evolved sophisticated post-translational modifications to regulate protein function and numerous biological processes, including ubiquitination controlled by the coordinated action of ubiquitin-conjugating enzymes and deubiquitinating enzymes (Dubs). However, the function of deubiquitination in pathogenic fungi is largely unknown. Here, the distribution of Dubs in the fungal kingdom was surveyed and their functions were systematically characterized using the phytopathogen Fusarium graminearum as the model species, which causes devastating diseases of all cereal species world-wide. Our findings demonstrate that Dubs are critical for fungal development and virulence, especially the ubiquitin-specific protease 15 (Ubp15). Global ubiquitome analysis and subsequent experiments identified three important substrates of Ubp15, including the autophagy-related protein Atg8, the mitogen-activated protein kinase Gpmk1, and the mycotoxin deoxynivalenol (DON) biosynthetic protein Tri4. Ubp15 regulates the deubiquitination of the Atg8, thereby impacting its subcellular localization and the autophagy process. Moreover, Ubp15 also modulates the deubiquitination of Gpmk1 and Tri4. This modulation subsequently influences their protein stabilities and further affects the formation of penetration structures and the biosynthetic process of DON, respectively. Collectively, our findings reveal a previously unknown regulatory pathway of a deubiquitinating enzyme for fungal virulence and highlight the potential of Ubp15 as a target for combating fungal diseases.

Intratumoral metabolic heterogeneity by 18F-FDG PET/CT to predict prognosis for patients with thymic epithelial tumors.

BACKGROUND: The aim of the present study was to evaluate the impact of intratumoral metabolic heterogeneity and quantitative 18F-FDG PET/CT imaging parameters in predicting patient outcomes in thymic epithelial tumors (TETs). METHODS: This retrospective study included 100 patients diagnosed with TETs who underwent pretreatment 18F-FDG PET/CT. The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on PET/CT were measured. Heterogeneity index-1 (HI-1; standard deviation [SD] divided by SUVmean) and heterogeneity index-2 (HI-2; linear regression slopes of the MTV according with different SUV thresholds), were evaluated as heterogeneity indices. Associations between these parameters and patient survival outcomes were analyzed. RESULTS: The univariate analysis showed that Masaoka stage, TNM stage, WHO classification, SUVmax, SUVmean, TLG, and HI-1 were significant prognostic factors for progression-free survival (PFS), while MTV, HI-2, age, gender, presence of myasthenia gravis, and maximum tumor diameter were not. Subsequently, multivariate analyses showed that HI-1 (p < 0.001) and TNM stage (p = 0.002) were independent prognostic factors for PFS. For the overall survival analysis, TNM stage, WHO classification, SUVmax, and HI-1 were significant prognostic factors in the univariate analysis, while TNM stage remained an independent prognostic factor in multivariate analyses (p = 0.024). The Kaplan Meier survival analyses showed worse prognoses for patients with TNM stages III and IV and HI-1 ≥ 0.16 compared to those with stages I and II and HI-1 < 0.16 (log-rank p < 0.001). CONCLUSION: HI-1 and TNM stage were independent prognostic factors for progression-free survival in TETs. HI-1 generated from baseline 18F-FDG PET/CT might be promising to identify patients with poor prognosis.

Diagnostic value of 18F-PSMA-1007 PET/CT for predicting the pathological grade of prostate cancer.

This study was designed to evaluate the diagnostic efficacy of relevant parameters of 18F-prostate-specific membrane antigen (PSMA)-1007 PET/CT in predicting the pathological grade of primary prostate cancer. Briefly, a prospective analysis was performed on 53 patients diagnosed with prostate cancer by systematic puncture biopsy, followed by 18F-PSMA-1007 PET/CT examination prior to treatment within 10 d. The patients were grouped in accordance with the Gleason grading system revised by the International Association of Urology Pathology (ISUP). They were divided into high-grade group (ISUP 4-5 group) and low-grade group (ISUP 1-3 group). The differences in maximum standardized uptake value (SUVmax), tumor-to-background ratio (TBR), intraprostatic PSMA-derived tumor volume (iPSMA-TV), and intraprostatic total lesion PSMA (iTL-PSMA) between the high- and low-grade group were statistically significant (p < .001). No significant difference was found for mean standardized uptake value (SUVmean) between the high- and low-grade groups (Z = -1.131, p = .258). Besides, binary multivariate logistic regression analysis showed that only iPSMA-TV and iTL-PSMA were independent predictors of the pathological grading, for which the odds ratios were 18.821 [95% confidence interval (CI): 2.040-173.614, p = .010] and 0.758 (95% CI: 0.613-0.938, p = .011), respectively. The area under the ROC of this regression model was 0.983 (95% CI: 0.958-1.00, p < .001). Only iTL-PSMA was a significant parameter for distinguishing ISUP-4 and ISUP-5 groups (Z = -2.043, p = .041). In a nutshell, 18F-PSMA-1007 PET/CT has good application value in predicting the histopathological grade of primary prostate cancer. Three-dimensional volume metabolism parameters iPSMA-TV and iTL-PSMA were found to be independent predictors for pathological grade.

Predictive value of clinical characteristics and baseline 18F-FDG PET/CT quantization parameters in primary adrenal diffuse large B-cell lymphoma: a preliminary study.

Background: Primary adrenal diffuse large B-cell lymphoma (PA-DLBCL) is a rare occurrence, has a very poor prognosis, and is marked by a high risk of relapse. Accurate prediction of patient prognosis before treatment initiation, along with timely adjustment of the treatment plan, holds paramount importance. 2-Deoxy-2-[fluorine-18]-fluoro-D-glucose (18F-FDG) positron emission tomography combined with computed tomography (PET/CT) imaging techniques are conventionally performed prior to treatment initiation in DLBCL patients, offering indispensable functional and metabolic insights into lymphoma lesions. Methods: We conducted a retrospective case-control study using data collected from January 2014 to December 2022, including 24 patients diagnosed with PA-DLBCL. Clinical information of patients was collected based on inpatient medical records, including age, gender, B symptoms, adrenocorticotropic hormone (ATCH), lactate dehydrogenase (LDH), ß2-microglobulin, albumin (Alb), ferritin (Fe), blood calcium, Eastern Cooperative Oncology Group performance status (ECOG-PS), International Prognostic Index, Ann Arbor staging, number of involved organs, and Hans' algorithm. Prior to treatment, all patients underwent baseline 18F-FDG PET/CT, and the metabolic parameters of the tumor were calculated using a threshold of 41% of maximum standardized uptake value (SUVmax), including metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Prognostic analysis of overall survival (OS) was performed using Kaplan-Meier survival analysis, as well as univariate and multifactor Cox proportional hazards regression models. Results: The 24 enrolled patients comprised 16 men and 8 women (median age 65 years, range 51-90 years). The median follow-up period was 17.5 months (range, 1-107 months). In univariate analysis, Ann Arbor stage, ß2-microglobulin, ATCH, number of involved organs, regions of lymph node involvement, treatment, chemotherapy cycles, SUVmax, MTV, and TLG showed association with OS (P<0.1). In multivariate analysis, Ann Arbor stage, ß2-microglobulin, ATCH, number of involved organs, and treatment were shown to be independent prognostic factors for OS. We found that SUVmax, MTV, and TLG correlated with Ann Arbor staging (P<0.05), mean standardized uptake value (SUVmean) and TLG correlated with the number of involved organs (P<0.05). Conclusions: PA-DLBCL is characterized by a low incidence and a poor prognosis. Baseline 18F-FDG PET/CT quantization parameters showed correlations with Ann Arbor staging and number of involved organs. Increasing the sample size or prolonging the follow-up period may reveal the predictive value of PET/CT quantization parameters.