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These findings provide new insights into the role of COMT Val158Met gene polymorphism in brain function, particularly its female-specific nature.Objective To investigate the dual mechanism of islet transplantation in T1D by regulating the immune tolerance of macrophages and inducing the neovascularization. Methods NC group, T1D model group and T1D model + islet group were constructed. Then, the abdominal aorta blood of abdominal aorta and islet tissue were collected. ELISA was performed to detect the level of IL-1Rα, IL-1α, IL-1β, CXCL2, MCP1, TNF-α and IL-10. Flow cytometry was used to measure the content of M1 and M2 macrophages. HE staining indicated the pathological characteristics of islet. IHC and WB were applied to determine the protein levels of IGF1R, FGFR2 or VEGFA as well as IGF1R, GRB2, EGFR, PTPN1, JAK2, STAT3, Caspase-1, Bcl2 respectively. Results Islet transplantation in T1D stimulated the expression of IL-1Rα, IL-1α, IL-1β, CXCL2, MCP1, TNF-α and IL-10 in abdominal aorta blood, changed the content of MHCII+CD206-M1 and MHCII+CD206+M2 macrophages, reduced the pathological features and the infiltration of immunocytes, promoted the expression of IGF1R, FGFR2 and VEGFA, eliminated cell apoptosis and induced the neovascularization in islet grafts. Conclusions Islet transplantation is an effective strategy for the treatment of T1D. It can increase the content of M2 macrophages whose immune tolerance can elevate the survival of islet grafts, reduce the inflammatory responses mediated by macrophages, promote the neovascularization and eliminate the cell apoptosis of islet grafts.Epigenetic factors play crucial roles in carcinogenesis by modifying chromatin architecture. Here, we established an epigenetic biosignature-based model for examining survival in patients with lung adenocarcinoma (LUAD). We retrieved gene-expression profiles and clinical data from The Cancer Genome Atlas and Gene Expression Omnibus and clustered the data into training (n = 490) and Validation (n = 226) datasets, respectively. To establish an epigenetic model, we identified prognostic epigenetic regulation-related genes by LASSO and Cox regression analyses, and established a novel 11-gene signature, including EPC1, GADD45A, HCFC2, RCOR1, SMARCAL1, TLE2, TRIM28, and ZNF516, for predicting LUAD overall survival (OS). The biosignature performed optimally in both the training and validation sets according to receiver operating characteristic and calibration plots. Moreover, the biosignature classified patients into high- and low-risk clusters with distinct survival times, with Cox regression analysis revealing the biosignature as an independent LUAD prognostic index. Furthermore, the generated nomogram integrating the prognostic gene biosignature and clinical indices predicted LUAD OS with high efficiency and outperformed tumor-node-metastasis staging in LUAD survival prediction. These results demonstrated the efficacy of the epigenetic signature prognostic nomogram for reliably predicting LUAD OS and its potential application for informing clinical decision making and individualized treatment.Our objectives were to evaluate 1) the associations of cognitive frailty with various health outcomes including disability, hospitalization, and death; 2) whether the associations differed by multimorbidity. We included data of 5113 Chinese older adults (aged 60+ years) who had baseline cognition and physical frailty assessments (2011 wave) and follow-up for 4 years. About 16.0% (n=820) had cognitive impairment; 6.7% (n=342) had physical frailty; and 1.6% (n=82) met criteria for cognitive frailty. Both cognitive impairment (odds ratios (ORs) range 1.41 to 2.11) and physical frailty (ORs range 1.51 to 2.43) were independently associated with basic activities of daily living (BADL), instrumental ADL (IADL), mobility disability, hospitalization, and death among participants without that corresponding outcome at baseline, even after accounting for covariates. Relative to participants who had normal cognition and were nonfrail, those with cognitive frailty had the highest risk for IADL disability (OR=3.40, 95% CI, 1.23-9.40) and death (OR=3.89, 95% CI, 2.25-6.47). We did not find significant interaction effects between cognitive frailty and multimorbidity (Pinteractions>0.05). Overall, cognitive frailty was associated with disability and death, independent of multimorbidity. This highlights the importance of assessing cognitive frailty in the community to promote primary and secondary preventions for healthy aging.Predicting recurrent intracerebral hemorrhage (ICH) related to cerebral amyloid angiopathy (CAA) currently relies on brain images. We aimed to investigate whether blood neurodegenerative biomarkers predict disease severity and ICH recurrence in CAA. We recruited 68 first probable CAA-ICH cases from a Chinese prospective cohort, and 95 controls. We used the single-molecule array to measure acute phase blood amyloid-40, amyloid-42, total tau and neurofilament light chain (NfL). We used multivariable Cox regression models to assess the association between blood biomarkers and CAA-ICH recurrence, and used the concordance (c-) index to assess prediction models. Blood amyloid-42/40, total tau, and NfL levels changed in CAA-ICH cases than controls. During a median follow-up of 2.4 years, NfL was associated with CAA-ICH recurrence (adjusted hazard ratio 2.14, 95% CI 1.57-2.93) independent of MRI burden of small vessel disease (SVD). The performance of a model to predict CAA-ICH recurrence using MRI burden of SVD alone (c-index 0.77) increased with the addition of NfL (c-index 0.88, 95% CI 0.73-1.00, p=0.019). Further, NfL was associated with baseline ICH volume, NIHSS and 6-month mRS score. find more Blood NfL is associated with severity and prognosis of CAA-ICH and is a promising addition to MRI burden of SVD to predict CAA-ICH recurrence.Demethoxycurcumin (DMC) has anti-glioma effects in vitro and in subcutaneous xenotransplanted tumors. Our previous study confirmed that the molecule also has mild anti-glioma effects on orthotopic glioblastomas in vivo. In this study, we found that DMC-BH, a DMC analogue, exhibited more potent in vitro and in vivo activities than did DMC. DMC-BH was cytotoxic against various glioma cells including SHG-44, C6, U251, U87, A172 and primary glioma cells. DMC-BH activity was characterized by low acute toxicity and an appropriate pharmacokinetic profile. We evaluated the anti-tumor effects of DMC-BH in an ectopic xenograft model, an orthotopic glioblastoma xenograft model and a patient-derived tumor xenograft (PDTX) model. DMC-BH exhibited potent anti-tumor activity in both the ectopic xenograft and PDTX models. Indeed, bioluminescence measurements showed that DMC-BH exerted a significantly greater anti-tumor effect on orthotopic glioma growth than DMC. Immunohistochemical analysis revealed that DMC-BH inhibited expression of Ki67 and increased the incidence of TUNEL-positive cells.