Attention deficit hyperactivity disorder (ADHD), a prevalent neurodevelopmental disorder influenced by both genetic and environmental factors, remains poorly understood regarding how its polygenic risk score (PRS) impacts functional networks and symptomology. This study capitalized on data from 11,430 children in the Adolescent Brain Cognitive Development study to explore the interplay between PRS_ADHD, brain function, and behavioral problems, along with their interactive effects. The results showed that children with a higher PRS_ADHD exhibited more severe attention deficits and rule-breaking problems, and experienced sleep disturbances, particularly in initiating and maintaining sleep. We also identified the central executive network, default mode network, and sensory-motor network as the functional networks most associated with PRS and symptoms in ADHD cases, with potential mediating roles. Particularly, the impact of PRS_ADHD was enhanced in children experiencing heightened sleep disturbances, emphasizing the need for early intervention in sleep issues to potentially mitigate subsequent ADHD symptoms.
Humans ; Attention Deficit Disorder with Hyperactivity/physiopathology* ; Male ; Female ; Sleep Wake Disorders/physiopathology* ; Adolescent ; Child ; Brain/diagnostic imaging* ; Multifactorial Inheritance ; Genetic Predisposition to Disease

Objective To explore the effect and mechanism of microRNA-133a-3p(miR-133a-3p)on invasion and apoptosis of breast cancer cells through targeted regulation of cullin-associated NEDD8-dissociated 1(CAND1).Methods MCF-7 cells were divided into overexpression group(mimics miR-133 a-3p transfection),NC group(mimics control transfection),co-transfection group(mimics miR-133a-3p transfection with pcDNA-CAND1 co-transfection)and control group(only adding the same amount of transfection reagents).Flow cytometry was used to detect cell apoptosis,Transwell assay was used to detect cell invasion,and real-time fluorescence quantitative polymerase chain reaction was used to detect miR-133a-3p and CAND1 expression.Results After transfection,the expression levels of miR-133a-3p in control group,NC group,overexpression group and co-transfection group were 0.50±0.08,0.51±0.09,1.06±0.10 and 1.05±0.15,respectively;the expression of CAND1 mRNA were 0.91±0.09,0.91±0.07,0.80±0.10 and 1.21±0.10,respectively.There were statistically significant differences in the above indexes between the co-transfection group and the control group,the NC group(all P＜0.05),and there were statistically significant differences between the overexpression group and the control group,the NC group(all P＜0.05).The apoptosis rates in control group,NC group,overexpression group and co-transfection group were(7.88±1.62)％,(8.87±2.01)％,(53.41±5.46)％,(29.54±3.78)％,respectively.The number of invasive cells in control group,NC group,overexpression group and co-transfection group were 161.02±10.31,155.87±12.30,85.21±9.11 and 118.37±10.84,respectively.There were statistically significant differences in the above indexes between transfection group and overexpression group,control group and NC group(all P＜0.05),and there were statistically significant differences between overexpression group and control group and NC group(all P＜0.05).Conclusion Overexpression of miR-133a-3p in human breast cancer cells MCF-7 can inhibit CAND1 and promote apoptosis and invasion of MCF-7 cells.

Objective:To investigate the association between high-density lipoprotein cholesterol (HDL-C) and the risk of diabetes mellitus (DM) in Chinese adults.Methods:This study was a secondary analysis of a multicenter, retrospective cohort study using data from the Chinese health screening program in the DATADRYAD database. Between 2010 and 2016, 211833 Chinese adults aged 20 years or older were screened for diabetes at baseline in 32 sites and 11 cities across the country. Baseline HDL-C level was the target independent variable and the risk of DM at follow-up was the dependent variable. Cox proportional hazards regression analysis assessed the independent association between HDL-C levels and the risk of developing DM. In this paper, the generalized Additive Model (GAM) and the smoothing curve fitting method were used to study the nonlinear relationships. In addition, subgroup analyses were conducted to assess the consistency of the correlations among different subgroup and to further validate the reliability of the results.Results:After adjusting for potential confounding factors such as age, sex and body mass index, HDL-C level was positively correlated with the development of diabetes ( HR=1.43, 95% CI: 1.08-1.90, P=0.012). The level of HDL-C showed a non-linear relationship with the risk of DM, and the inflection point was 1.81 mmol/L. The HR (95% CI) of the left and right sides of the inflection point were 0.94 (0.56-1.55) and 2.54 (1.93-3.30), respectively. When HDL-C>1.81 mmol/L, HDL-C was positively correlated with the occurrence of DM. Each 1.00 mmol/L increase in HDL-C increased the risk of diabetes mellitus by 1.54 times ( P<0.001); when HDL-C<1.81 mmol/L, the risk of diabetes decreased by 6% for every 1.00 mmol/L increase in HDL-C ( P=0.798). Subgroup analysis showed that, in the age, male, BMI 24.5-52.7 kg/m 2 subgroups, all the systolic blood pressure subgroups, diastolic blood pressure 69-77 and 78-164 mmHg (1 mmHg=0.133 kPa) subgroups, total cholesterol 0.02-4.26 and 5.00-17.84 mmol/L subgroups, all the triglyceride subgroups, low-density lipoprotein 0-2.42 and 2.99-12.60 mmol/L subgroups, alanine aminotransferase 23.4-1 508.4 U/L subgroups, aspartate transaminase 0-19.7 and 24.8-1 026.2 U/L subgroups, all the urea nitrogen subgroups, creatinine 61.5-76.9, 77.0-1 116.6 μmol/L subgroups, never smoking subgroup, subgroup with frequent alcohol consumption or family history of diabetes mellitus, the effect values of HDL-C and the risk of diabetes mellitus in Chinese adults showed good stability (all HR>1.00). Conclusions:High levels of HDL-C are associated with an increased risk of DM in Chinese adults. When HDL-C is greater than 1.81 mmol/L, HDL-C is positively correlated with DM.

Objective:To analyze the clinical phenotype and genetic etiology of a child with Multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1).Methods:Clinical data of a 2-year-old boy who had presented at the Affiliated Hospital of Qingdao University in March 2023 for "intermittent limb twitching for 2 years" was collected. Peripheral blood samples were collected from the child and his parents for whole-exome sequencing (WES). Candidate variants were verified by Sanger sequencing and bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).Results:The child had manifested with distinctive facial features, limb deformities, hypotonia, motor and intellectual delays, and epileptic seizures. WES revealed that he has harbored compound heterozygous variants of the PIGN gene, namely c. 963G>A (p.Q321=) and c. 994A>T (p.I332F), which were inherited from his phenotypically normal mother and father, respectively. Based on the ACMG guidelines, the c. 963G>A was classified as a pathogenic variant (PVS1+ PM2_Supporting+ PM3), whilst the c. 994A>T was classified as a variant of uncertain significance (PM2_Supporting+ PP3). Conclusion:Above discovery has expanded the mutational spectrum of the PIGN gene variants associated with MCAHS1, which may facilitate delineation of its genotype-phenotype correlation.

Objective To construct curcumin pyrazole derivative by the reaction of diketone of curcumin and benzylhydrazine based on the above structure-activity relationship,and to explore its antioxidant activity to provide experimental basis for the development of curcumin antioxidant derivative.Methods Curcumin-N-substituted pyrazole derivative was synthesized from curcumin and benzylhydrazine.The structures of the derivative were confirmed by infrared spectroscopy(IR),nuclear magnetic resonance spectroscopy(1H-NMR,13C-NMR)and LC-MS.The antioxidant activity in vitro of the derivative was evaluated by determination of curcumin and its pyrazole derivative scavenging ability for 2,2-diphenyl-1-picrylhydrazyl(DPPH)free radical and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid(ABTS)free radical.Results Curcumin pyrazole derivative was successfully synthesized.Curcumin and its pyrazole derivative showed good free radical scavenging effects in the range of 4.6-73.6,6.25-100 μg·mL-1,respectively,with a significant dose-effect relationship.The half-maximal inhibition(IC50)values of curcumin and its pyrazole derivatives determined by DPPH method were 14.24,40.37 μg·mL-1,respectively,while the IC50 values of curcumin and its pyrazole derivatives determined by ABTS method were 36.65,19.26 μg·mL-1,respectively.Conclusion The antioxidant activity of β-dione of curcumin was retained through the substitution of the pyrazole ring,and the curcumin pyrazole derivative deserves further investigation as a potential antioxidant.

Cholangiocarcinoma originates from bile duct epithelial cells and is a highly heterogeneous and aggressive malignant tumour. A deep understanding of the biological characteristics of the tumor can help to make progress in the treatment of cholangiocarcinoma. There are many types of animal models of cholangiocarcinoma, and different models can be induced according to different research purposes, including chemotoxic agent models, cholestatic models, implantation models, genetically engineered models, etc. This paper summarises the existing animal models of cholangiocarcinoma, compares their advantages and disadvantages as well as the application scenarios, and provides a reference for subsequent studies.

Blueberries are rich in phenolic compounds including anthocyanins which are closely related to biological health functions. The purpose of this study was to investigate the antioxidant activity of blueberry anthocyanins extracted from 'Brightwell' rabbiteye blueberries in mice. After one week of adaptation, C57BL/6J healthy male mice were divided into different groups that were administered with 100, 400, or 800 mg/kg blueberry anthocyanin extract (BAE), and sacrificed at different time points (0.1, 0.5, 1, 2, 4, 8, or 12 h). The plasma, eyeball, intestine, liver, and adipose tissues were collected to compare their antioxidant activity, including total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity and glutathione-peroxidase (GSH-PX/GPX) content, and the oxidative stress marker malondialdehyde (MDA) level. The results showed that blueberry anthocyanins had positive concentration-dependent antioxidant activity in vivo. The greater the concentration of BAE, the higher the T-AOC value, but the lower the MDA level. The enzyme activity of SOD, the content of GSH-PX, and messenger RNA (mRNA) levels of Cu,Zn-SOD, Mn-SOD, and GPX all confirmed that BAE played an antioxidant role after digestion in mice by improving their antioxidant defense. The in vivo antioxidant activity of BAE indicated that blueberry anthocyanins could be developed into functional foods or nutraceuticals with the aim of preventing or treating oxidative stress-related diseases.
Male ; Mice ; Animals ; Antioxidants/pharmacology* ; Blueberry Plants ; Anthocyanins/pharmacology* ; Mice, Inbred C57BL ; Superoxide Dismutase ; Plant Extracts/pharmacology* ; Superoxide Dismutase-1

Gray Matter/diagnostic imaging* ; Cerebral Cortex ; Brain ; Magnetic Resonance Imaging