Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

Objective: To explore the difference in intensive care unit (ICU) readmission rate between high dependency unit (HDU) and general ward for the patients with severe liver disease (SLD), and reflect the effect of HDU on SLD patientse. Methods: A clinical cohort of patients transferred out of ICU was established, and patients with severe liver disease who were transferred to HDU& general ward from July 2017 to December 2021 in the intensive care Unit of the Fifth Medical Center of PLA General Hospital were continuously enrolled. The main liver function indexes and MELD scores between the two groups were compared. Analyze the differences in severity and ICU readmission rate of SLD patients transferred to different wards, and clarify the role of HDU in the management of SLD patient. Area under the receiver operating characteristic (AUROC) was used to investigate the value of MELD score in predicting the occurrence of return to ICU. Results: The level of INR, TB, ALT and MELD scores of SLD patients transferred to HDU were significantly higher than those of patients transferred to general ward (all P < 0.05). MELD > 17 was found in 70.7% of SLD patients transferred to HDU group, while MELD ≤ 17 was found in 61.9% of SLD patients in general ward group. The ICU readmission rate of all patients in this cohort was 11.4%. By MELD quartile stratification, patients with SLD whose MELD > 23 had a significantly higher ICU readmission rate (20.0%) than those with SLD whose MELD ≤ 23 (8.6%) (P = 0.020). The ICU readmission rate was 8.2% when MELD ≤ 23 in the HDU group and 9.1% when MELD > 23, showing no significant difference (P = 1.000). The ICU readmission rate was 8.8% when MELD ≤ 23 in the general ward group. ICU reentry rate increased significantly to 36.4% when MELD > 23 (P = 0.001). MELD Score predicts that the optimal cut-off value of SLD patients in general ward readmitted to ICU was 23.5. Conclusion: The high dependency unit could better admit patients with SLD who were transferred out of ICU and required step-down treatment, and significantly reduced the ICU readmission rate of patients with SLD who were transferred out of ICU with MELD > 23. The patients with SLD and MELD score > 23 are suitable to be transferred from ICU to HDU.

As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified

Objective: To explore the interaction effect between mother's educational level and preschoolers' dietary pattern on attention-deficit/hyperactivity disorder (ADHD). Methods: In 2014, there were 16 439 children aged 3-6 years old from 91 kindergartens in Ma'anshan municipality of China. A semi-quantitative food frequency questionnaire and the 10-item Chinese version of the Conners' Abbreviated Symptom Questionnaire (C-ASQ) were administered to assess the usual dietary intake and symptoms on ADHD. Social-demographic information was collected through questionnaires. Unconditional logistic regression was used to analyze the multiplication interaction effect between mother's educational level and preschoolers' dietary pattern on ADHD. Excel software was used to analyze the additive interaction effect of mother's educational level and preschoolers'dietary pattern on ADHD. Results: Results showed that factors as: mother's low educational level[aOR=1.31 (1.13-1.52)], scores related to preschoolers in the top quintile of "food processing" [aOR=1.31 (1.16-1.48)] and "snack" [aOR=1.45 (1.29-1.63)]patterns showed greater odds while preschoolers in the top quintile of "vegetarian" [aOR=0.80 (0.71-0.90)]showed less odds for having ADHD symptoms. Both multiplication and additive interactions were observed between mothers with less education. The processed dietary patterns (OR=1.17, 95%CI: 1.11-1.25), relative excess risk of interaction (RERI), attributable proportion (AP) and the interaction index (SI) appeared as 0.21, 0.13 and 1.47, respectively. Multiplication interaction was observed between levels of mother's low education and the snack dietary pattern (OR=1.21, 95%CI: 1.14-1.29), with RERI, AP and SI as 0.49, 0.26 and 2.36, respectively. However, neither multiplication interaction or additive interaction was noticed between levels of mother's low education and the vegetarian dietary pattern (OR=0.97, 95%CI: 0.92-1.03), with RERI, AP and SI as 0.09, 0.05 and 1.15, respectively. Conclusions: Levels of mother's low education presented a risk factor for ADHD symptoms in preschool children. Both multiplication interaction and additive interaction were observed between mother's low education levels and the processed dietary pattern. Multiplication interaction was noticed between mother's education levels and the snack dietary pattern but not with the vegetarian dietary pattern.
Attention Deficit Disorder with Hyperactivity/epidemiology* ; Child ; Child Nutritional Physiological Phenomena ; Child, Preschool ; China ; Diet ; Educational Status ; Feeding Behavior ; Female ; Humans ; Logistic Models ; Mothers ; Risk Factors ; Surveys and Questionnaires