Pyroptosis-mediator GSDMD promotes Parkinson's disease pathology via microglial activation and dopaminergic neuronal death.

GSDMD-mediated pyroptosis occurs in the nigrostriatal pathway in Parkinson's disease animals, yet the role of GSDMD in neuroinflammation and death of dopaminergic neurons in Parkinson's disease remains elusive. Here, our in vivo and in vitro studies demonstrated that GSDMD, as a pyroptosis executor, contributed to glial reaction and death of dopaminergic neurons across different Parkinson's disease models. The ablation of the Gsdmd attenuated Parkinson's disease damage by reducing dopaminergic neuronal death, microglial activation, and detrimental transformation. Disulfiram, an inhibitor blocking GSDMD pore formation, efficiently curtailed pyroptosis, thereby lessening the pathology of Parkinson's disease. Additionally, a modification in GSDMD was identified in the blood of Parkinson's disease patients in contrast to healthy subjects. Therefore, the detected alteration in GSDMD within the blood of Parkinson's disease patients and the protective impact of disulfiram could be promising for the diagnostic and therapeutic approaches against Parkinson's disease.

A Diary Study of Daily Negative Aging Stereotypes and Goal Pursuit in Older Adults.

OBJECTIVES: This study aimed to investigate the association between negative aging stereotypes and goal pursuit in daily life among older adults. We also explored the roles of stereotype threat and stereotype challenge reactions in mediating this association. Additionally, this study investigated whether variations in these associations exist among older adults based on their self-integrity levels. METHODS: Participants were 100 older adults who completed daily measures assessing negative aging stereotype experiences, threat and challenge reactions, goal pursuit activities, and self-integrity over a week. RESULTS: More daily experiences of negative aging stereotypes were associated with greater avoidance of responsibilities in goal pursuit and less progress toward goals. Increased threat reactions and decreased challenge reactions were mediators of the association between stereotype experiences and avoidance of responsibilities, as well as that between stereotype experiences and progress toward goals, respectively. Moreover, the associations between threat reactions and avoidance of responsibilities as well as between stereotype experiences and challenge reactions were more pronounced in older adults with lower self-integrity levels. DISCUSSION: This study is pioneering in demonstrating the real-life interplay between aging stereotypes and goal pursuit among older adults. Its findings not only expand upon the literature concerning aging stereotypes, but also offer theoretical insights for the development of interventions aimed at goal pursuit. These insights have significant implications for fostering healthy aging.

Predictive value of delta radiomics in xerostomia after chemoradiotherapy in patients with stage III-IV nasopharyngeal carcinoma.

BACKGROUND: Xerostomia is one of the most common side effects in nasopharyngeal carcinoma (NPC) patients after chemoradiotherapy. To establish a Delta radiomics model for predicting xerostomia secondary to chemoradiotherapy for NPC based on magnetic resonance T1-weighted imaging (T1WI) sequence and evaluate its diagnostic efficacy. METHODS: Clinical data and Magnetic resonance imaging (MRI) data before treatment and after induction chemotherapy (IC) of 255 NPC patients with stage III-IV were collected retrospectively. Within one week after CCRT, the patients were divided into mild (92 cases) and severe (163 cases) according to the grade of xerostomia. Parotid glands in T1WI sequence images before and after IC were delineated as regions of interest for radiomics feature extraction, and Delta radiomics feature values were calculated. Univariate logistic analysis, correlation, and Gradient Boosting Decision Tree (GBDT) methods were applied to reduce the dimension, select the best radiomics features, and establish pretreatment, post-IC, and Delta radiomics xerostomia grading predictive models. The receiver operating characteristic (ROC) curve and decision curve were drawn to evaluate the predictive efficacy of different models. RESULTS: Finally, 15, 10, and 12 optimal features were selected from pretreatment, post-IC, and Delta radiomics features, respectively, and a xerostomia prediction model was constructed with AUC values of 0.738, 0.751, and 0.843 in the training set, respectively. Only age was statistically significant in the clinical data of both groups (P < 0.05). CONCLUSION: Delta radiomics can predict the degree of xerostomia after chemoradiotherapy for NPC patients and it has certain guiding significance for clinical early intervention measures.

Early prediction of long-term survival of patients with nasopharyngeal carcinoma by multi-parameter MRI radiomics.

Purpose: The objective is to create a comprehensive model that integrates clinical, semantic, and radiomics features to forecast the 5-year progression-free survival (PFS) of individuals diagnosed with non-distant metastatic Nasopharyngeal Carcinoma (NPC). Methods: In a retrospective analysis, we included clinical and MRI data from 313 patients diagnosed with primary NPC. Patient classification into progressive and non-progressive categories relied on the occurrence of recurrence or distant metastasis within a 5-year timeframe. Initial screening comprised clinical features and statistically significant image semantic features. Subsequently, MRI radiomics features were extracted from all patients, and optimal features were selected to formulate the Rad-Score.Combining Rad-Score, image semantic features, and clinical features to establish a combined model Evaluation of predictive efficacy was conducted using ROC curves and nomogram specific to NPC progression. Lastly, employing the optimal ROC cutoff value from the combined model, patients were dichotomized into high-risk and low-risk groups, facilitating a comparison of 10-year overall survival (OS) between the groups. Results: The combined model showcased superior predictive performance for NPC progression, reflected by AUC values of 0.84, an accuracy rate of 81.60%, sensitivity at 0.77, and specificity at 0.81 within the training group. In the test set, the AUC value reached 0.81, with an accuracy of 74.6%, sensitivity at 0.82, and specificity at 0.66. Conclusion: The amalgamation of Rad-Score, clinical, and imaging semantic features from multi-parameter MRI exhibited significant promise in prognosticating 5-year PFS for non-distant metastatic NPC patients. The combined model provided quantifiable data for informed and personalized diagnosis and treatment planning.

Janus hydrogel loaded with a CO2-generating chemical reaction system: Construction, characterization, and application in fruit and vegetable preservation.

In this study, we inserted a dynamic chemical reaction system that can generate CO2 into Janus hydrogel (JH) to develop a multidimensional preservation platform that integrates hygroscopicity, antibacterial activity, and modified atmospheric capacity. The double gel system developed using sodium alginate/trehalose at a 1:1 ratio effectively encapsulated 90% of citric acid. Furthermore, CO2 loss was avoided by separately embedding NaHCO3/cinnamon essential oil and citric acid microcapsules into a gelatin pad to develop JH. Freeze-dried JH exhibited a porous and asymmetric structure, very strongly absorbing moisture, conducting water, and rapidly releasing CO2 and essential oils. Furthermore, when preserving various fruits and vegetables in practical settings, JH provided several preservation effects, including color protection, microbial inhibition, and antioxidant properties. Our study findings broaden the application of JH technology for developing chemical reaction systems, with the resulting JH holding substantial promise for cold chain logistics.