The alpha-2A-adrenergic receptor gene polymorphism modulates gray matter structural networks, visual memory, and inhibitory cognitive control in children with attention deficit/hyperactivity disorder.

The ADRA2A-1291 C > G polymorphism and deficits in visual memory and inhibitory control were associated with attention deficit hyperactivity disorder (ADHD). The present study aimed to examine whether the ADRA2A G/G genotype affected gray matter (GM) networks in ADHD and whether these gene-brain modulations were associated with cognitive function in ADHD. Seventy-five drug-naïve ADHD children and 70 healthy controls were recruited. The GM networks were obtained based on areal similarities of GM, and network topological properties were analyzed using graph theory. Visual memory and inhibitory control were assessed by the visual memory test and the Stroop test, respectively. SNP genotyping of rs1800544 was performed. A significant interaction between ADHD diagnosis and gene polymorphism was observed in the nodal degree of the left inferior parietal lobule and left inferior (opercular) frontal gyrus. In the ADHD group, nodal efficiency in the left inferior (orbital) frontal gyrus in ADHD with G/G was lower than that in ADHD without G/G. Moreover, the ADRA2A-modulated alterations in nodal properties were associated with visual memory and inhibitory control. Our findings provide novel gene-brain behavior association evidence that GM network alterations, especially in the frontoparietal loop, were related to visual memory and inhibitory control in ADHD children with ADRA2A-G/G.

circGRAMD1B contributes to migration, invasion and epithelial-mesenchymal transition of lung adenocarcinoma cells via modulating the expression of SOX4.

Lung adenocarcinoma (LUAD) represents the subtype of non-small-cell lung cancer (NSCLC), with the high morbidity over the world. Mounting studies have highlighted the important roles of circular RNAs (circRNA) in cancers, including LUAD. This study mainly focused on revealing the role of circGRAMD1B and its relevant regulatory mechanism in LUAD cells. RT-qPCR and Western blot were conducted to detect the expression of target genes. Function assays were performed to determine the effect of related genes on migration, invasion, and epithelial-mesenchymal transition (EMT) of LUAD cells. Mechanism analyses were conducted to figure out the specific mechanism with regard to circGRAMD1B and its downstream molecules as well. Based on the experimental results, circGRAMD1B was upregulated in LUAD cells and promoted the migration, invasion, and EMT of LUAD cells. Mechanically, circGRAMD1B sponged miR-4428 to upregulate the expression of SOX4. In addition, SOX4 activated the expression of MEX3A at the transcriptional level, thereby modulating PI3K/AKT pathway to facilitate LUAD cell malignant behaviors. In conclusion, circGRAMD1B is discovered to modulate miR-4428/SOX4/MEX3A axis to further activate PI3K/AKT pathway, finally boosting migration, invasion, and EMT of LUAD cells.

Altered single-subject gray matter structural networks in drug-naïve attention deficit hyperactivity disorder children.

Altered topological organization of brain structural covariance networks has been observed in attention deficit hyperactivity disorder (ADHD). However, results have been inconsistent, potentially related to confounding medication effects. In addition, since structural networks are traditionally constructed at the group level, variabilities in individual structural features remain to be well characterized. Structural brain imaging with MRI was performed on 84 drug-naïve children with ADHD and 83 age-matched healthy controls. Single-subject gray matter (GM) networks were obtained based on areal similarities of GM, and network topological properties were analyzed using graph theory. Group differences in each topological metric were compared using nonparametric permutation testing. Compared with healthy subjects, GM networks in ADHD patients demonstrated significantly altered topological characteristics, including higher global and local efficiency and clustering coefficient, and shorter path length. In addition, ADHD patients exhibited abnormal centrality in corticostriatal circuitry including the superior frontal gyrus, orbitofrontal gyrus, medial superior frontal gyrus, precentral gyrus, middle temporal gyrus, and pallidum (all p < .05, false discovery rate [FDR] corrected). Altered global and nodal topological efficiencies were associated with the severity of hyperactivity symptoms and the performance on the Stroop and Wisconsin Card Sorting Test tests (all p < .05, FDR corrected). ADHD combined and inattention subtypes were differentiated by nodal attributes of amygdala (p < .05, FDR corrected). Alterations in GM network topologies were observed in drug-naïve ADHD patients, in particular in frontostriatal loops and amygdala. These alterations may contribute to impaired cognitive functioning and impulsive behavior in ADHD.

Microstructural abnormalities of the brain white matter in attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is an early-onset neurodevelopmental disorder with multiple behavioural problems and executive dysfunctions for which neuroimaging studies have reported a variety of abnormalities, with inconsistencies partly owing to confounding by medication and concurrent psychiatric disease. We aimed to investigate the microstructural abnormalities of white matter in unmedicated children and adolescents with pure ADHD and to explore the association between these abnormalities and behavioural symptoms and executive functions. METHODS: We assessed children and adolescents with ADHD and healthy controls using psychiatric interviews. Behavioural problems were rated using the revised Conners' Parent Rating Scale, and executive functions were measured using the Stroop Colour-Word Test and the Wisconsin Card Sorting test. We acquired diffusion tensor imaging data using a 3 T MRI system, and we compared diffusion parameters, including fractional anisotropy (FA) and mean, axial and radial diffusivities, between the 2 groups. RESULTS: Thirty-three children and adolescents with ADHD and 35 healthy controls were included in our study. In patients compared with controls, FA was increased in the left posterior cingulum bundle as a result of both increased axial diffusivity and decreased radial diffusivity. In addition, the averaged FA of the cluster in this region correlated with behavioural measures as well as executive function in patients with ADHD. LIMITATIONS: This study was limited by its cross-sectional design and small sample size. The cluster size of the significant result was small. CONCLUSION: Our findings suggest that white matter abnormalities within the limbic network could be part of the neural underpinning of behavioural problems and executive dysfunction in patients with ADHD.

High selectivity of PI3Kß inhibitors in SETD2-mutated renal clear cell carcinoma.

PURPOSE: Clear cell renal cell carcinoma (ccRCC) is characterized with frequent mutations of SETD2 gene and our purpose was to explore targeted therapy for this entity. METHODS: By bioinformatic investigation of two major databases, the Genomics of Drug Sensitivity in Cancer (GDSC) database and The Cancer Genome Atlas (TCGA) database, we identified the selective PI3Kß inhibitors TGX221 and AZD6482 as selective inhibitors for ccRCC with SETD2 mutations, with AZD6482 additionally targeting PIK3CA and CDK6 mutations. RESULTS: Further investigation on AZD6482 profile revealed that mutations in RB1, KRAS, NRAS and APC contributed in drug resistance. Changes in both AZD6482-sensitive and -resistant gene sets showed limited impact on prognosis. Western blotting showed AZD6482 did not induce changes in a panel of major downstream effectors of AKT, but substantially increased PMS2 level. AZD6482 also selectively inhibited migration, invasiveness, and colony formation of ccRCC cells with SETD2 mutations. Integrative network analysis revealed complex interactions between these genes except SETD2. CONCLUSION: AZD6482 is a novel inhibitor with high selectivity for ccRCC SETD2 mutations. Increased activity of PI3K/AKT/PMS2 could play a role in SETD2 mutated ccRCC.

An Ultrasonographic Analysis of the Deep Inferior Tendon in the Masseter Muscle: Implications for Botulinum Toxin Injections.

(1) Background: With the increasing aesthetic pursuit of facial features, the clinical use of Botulinum Toxin Type A (BoNT-A) injections for masseter hypertrophy has been on the rise. However, due to variations in masseter muscle structure and differences in clinicians' injection techniques, blind injections may lack precision, potentially compromising treatment accuracy and increasing the risk of complications. (2) Objectives: The study aims to use ultrasonography to detail the deep inferior tendon (DIT) within the masseter muscle in a young Chinese cohort, refine its classification, analyze muscle belly thickness and variations across groups, and propose a customized ultrasound-guided BoNT-A injection protocol. (3) Methods: Ultrasound imaging was used to observe the bilateral masseter muscles at rest and during clenching. The features of the DIT were classified from these images, and the thickness of the masseter's distinct bellies associated with the DIT types was measured in both states. (4) Results: The study cohort included 103 participants (27 male, 76 female), with 30 muscles in the normal masseter group and 176 muscles in the hypertrophy group. The DIT was categorized as Type A, B (subtypes B1, B2), and C. The distribution of these types was consistent across normal, hypertrophic, and gender groups, all following the same trend (B > A > C). In hypertrophy, Type B1 showed uniform thickness across masseter bellies, B2 presented with a thinner intermediate belly, and Type C had mainly superficial muscle enlargement. Changes in muscle thickness during clenching were noted but not statistically significant among different bellies. (5) Conclusions: The study evidences individual variation in the DIT, highlighting the importance of precise DIT classification for effective BoNT-A injections. A tailored ultrasound-guided BoNT-A injection strategy based on this classification may enhance safety and efficacy of the therapy.

Diagnostic efficacy of quantitative ultrasonography for anterior disc displacement of the temporomandibular joint.

Background: Ultrasonography has been applied as an alternative method in the assessment of temporomandibular joint (TMJ) pathology including anterior disc displacement (ADD). However, a concrete screening or diagnostic method which is feasible in clinical practice has not yet been established. The study aimed to establish a quantitative ultrasonographic method and determine its diagnostic efficacy for ADD of the TMJ. Methods: A total of 75 joints were allocated to either the normal disc position (NDP) group or the ADD group using magnetic resonance imaging (MRI) as the reference standard. Longitudinal scans of the lateral articular compartment were obtained by a 14-MHz L-shaped linear array transducer. The width of the lateral joint space (LJS), the upper lateral joint space (ULJS), and the lower lateral joint space (LLJS), as well as the position of the lateral articular disc edge (ADE), were investigated by stepwise logistic regression analysis to identify significant indicators of ADD and to build a diagnostic model. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were computed at the optimal cut-off value. Results: MRI detected 25 joints in the NDP group and 50 joints in the ADD group. Correlation analysis indicated that all 4 variables were associated with ADD. With the best performance of the area under the receiver operating characteristic (ROC) curve (AUC) of 0.939, LJS and ULJS were identified as predictors of ADD and subsequently adopted to build a diagnostic model by stepwise logistic regression. The optimal cut-off value of the 2-variable regression model for diagnosing ADD was 0.800, with a sensitivity of 82%, specificity of 96%, PPV of 97.6%, NPV of 72.7%, and an accuracy of 86.7%. Conclusions: The quantitative ultrasonographic diagnostic method showed promising diagnostic efficacy. It has the potential to be used for ADD screening in future clinical practice.

[Comparison of Nitrogen and Phosphorus Uptake and Water Purification Ability of Five Submerged Macrophytes].

Uptake of nitrogen (N) and phosphorus (P) and their purification capacity for five native submerged macrophytes were investigated in laboratory simulated hydrostatic conditions,including Hydrilla verticillata,Vallisneria natans,Ceratophyllum demersum,Myriophyllum spicatum,Potamogeton maackianus.The results indicated that the moisture contents of different submerged macrophytes were almost the same before and after the test,with the range of 89.8%-92.0%.The net accumulated biomass changed from 1.52 g·m-2 to 12.92 g·m-2 among different submerged macrophytes,and the highest net accumulated biomass of Hydrilla verticillata was 8.5 times higher than the lowest plant of Potamogeton maackianus.The N and P contents of five submerged macrophytes ranged from 26.54 to 34.44g·kg-1 and from 2.54 to 4.01g·kg-1,respectively,and the N and P contents of Ceratophyllum demersum were relatively high.Total N and P removal efficiency of different submerged macrophyte treatments had ranges of 63.8%-83.1% and 49.2%-70.8%,significantly higher than those of the CK treatment (39.9% and 36.9%),respectively,and the removal efficiency decreased in the order of Hydrilla verticillata >Ceratophyllum demersum >Vallisneria natans >Myriophyllum spicatum >Potamogeton maackianus.Total N and P removal efficiencies of different submerged macrophyte treatments were significantly correlated with net accumulated biomass,with correlation coefficients of 0.994(P<0.01) and 0.996(P<0.01).The contribution of direct N and P uptake to different submerged macrophytes had the ranges of 1.5%-13.3% and 2.2%-13.2%,and the synergism contribution (deducting self-purification capacity of water) of different submerged macrophytes ranged 22.5%-29.9% and 10.1%-20.6%,indicating that the synergistic effect of submerged macrophytes purification was much more significant than the direct uptake effect in the process of water purification.

[Effects of sludge compost used as lawn medium on lawn growth and soil and water environment].

To address effect of the sludge compost-containing medium on the growth of Manila lawn and environment quality, a pot experiment was conducted using six treatments based on contrasting sludge compost addition volume ratios in the soil system (i. e., 0% , 10% , 25% , 50% , 75% and 100%). The results indicated that the growth potential of Manila lawn was increased with increasing sludge compost addition volume ratio. The content of Hg in Manila plant was significantly positively correlated with that in the lawn medium. Although the contents of Cr, Cd and Hg in the lawn medium were synchronously increased with increasing sludge compost addition volume ratio in the soil system, their contents were all lower than the critical levels of third-class standard in the National Soil Environmental Quality Standard. The heavy metal and nitrate concentrations detected in percolating water were significantly positively correlated with those in the lawn medium, respectively. When the sludge compost addition volume ratio was more than 50% in this study, both heavy metal and nitrate concentrations in percolating water would exceed the maximum allowable levels of the National Groundwater Environment Quality Standard.