Nowadays, the discovery and development of α-glucosidase inhibitors from natural products or their derivatives represents an attractive approach. Here we reported studies on a series of novel N-acyl-2-aminothiazoles fused (+)-nootkatone and evaluation for their α-glucosidase inhibitory activities. Most of (+)-nootkatone derivatives exhibited more potent α-glucosidase inhibitory ability than the positive drug acarbose. In particular, compounds II7 and II14 showed the most promising α-glucosidase inhibitory ability with IC50 values of 13.2 and 13.8 µM. II7 and II14 also exhibited relatively low cytotoxicities towards normal LO2 cells. Kinetic study indicated that compounds II7 and II14 inhibited the α-glucosidase in a noncompetitive manner, and molecular docking results were in line with the noncompetitive characteristics that II7 and II14 did not bind to the known active sites (Asp214, Glu276 and Asp349). Based on our findings, these (+)-nootkatone derivatives could be used as antidiabetic candidates.Increased anxiety sensitivity (AS), or the fear of anxiety-related cognitive, social, and physical symptoms which are misinterpreted as having harmful implications, has shown a relationship with substance use disorders. People with substance use disorders also experience addiction-related problems across domains of life functioning. However, few studies have evaluated the relationship between elevated AS and addiction-related problems across specific life areas. We evaluated, first, whether AS predicted addiction-related problems in a sample of treatment-refractory outpatients with opioid use disorders and, second, whether sex moderated the relationship between AS and addiction-related problems in this sample. Participants with treatment-refractory opioid use disorders (n = 92, 53.3% male) completed baseline assessments of AS (the Anxiety Sensitivity Index) and addiction-related problems (the Addiction Severity Index). Baseline AS total score was a significant independent predictor of both baseline Addiction Severity Index medical status (β = 0.29, t = 2.84, p = .006) and psychiatric status (β = 0.30, t = 2.99, p = .004) composite scores but was not associated with social, employment or legal difficulties. These findings were maintained when controlling for drug use severity, though baseline AS total score became a significant predictor of baseline legal difficulties (β = -0.23, t = -2.25, p = .027). There was no moderating role of sex on the relationship between baseline AS and addiction-related problems. Our findings suggest that, regardless of sex, elevated AS predicts increased addiction-related medical and psychiatric problems, and decreased legal problems when accounting for drug use severity, in outpatients with opioid use disorders.

Despite intense neuroscience research on the neurobiological underpinnings of Gambling Disorder (GD) and gambling-related decision-making, effective treatments targeting these dysfunctions are still lacking. Non Invasive Brain Stimulation (NIBS) techniques, such as transcranial Direct Current Stimulation (tDCS) and Transcranial Magnetic Stimulation (TMS), selectively modulate activity of brain circuits and have the potential to reverse alterations sustaining GD symptoms. Therefore, the aim of this systematic review was to determine the impact of different NIBS interventions on gambling-related decision processes.

We conducted a comprehensive and translational search in three online databases (MEDLINE via PubMed, Scopus, Web of Science), in accordance with the PRISMA guidelines. We included studies applying neuromodulation (TMS, tDCS) techniques in GD patients or assessing gambling-related decision-making in healthy subjects. In addition, we explored the potential impact of NIBS in drug-induced GD (e.g., Pinvestigate connectivity changes and laterality issues (unilateral versus bilateral; left versus right) of NIBS application in GD.

Gender bias in measures of cannabis problems may differentially affect how men and women endorse items. This gender invariance might mask, exaggerate, or otherwise obscure true distinctions in experiences of cannabis consequences.

The Cannabis-Associated Problems Questionnaire (CAPQ), a measure of interpersonal deficits, occupational impairment, psychological issues, and physical side effects related to cannabis use, contained items with gender-based differential item functioning (DIF) in previous work-a finding we aim to replicate and extend (Lavender, Looby, & Earleywine, 2008).

In a sample of 4053 cannabis users, gender differences were apparent in global scores on the CAPQ. A DIF analysis revealed two gender-biased items, including one identified previously. Removal of these items did not significantly alter the scale’s relation to cannabis use. Gender differences on the CAPQ persisted after removal of the two problematic items, indicating true gender differences still exist in men and women’s experiences of cannabis-related consequences. Gender appeared to significantly contribute to scores on the full CAPQ and the short-form of the CAPQ with biased item removed, even after controlling for indices of cannabis use.

These findings suggest that the CAPQ evidences less gender bias than previously thought, perhaps due to diminishing gender-based stereotypes. Future work might opt to use the short form of the CAPQ to minimize gender-based DIF. In addition, potential biases in measures of substance use problems deserve more attention.

These findings suggest that the CAPQ evidences less gender bias than previously thought, perhaps due to diminishing gender-based stereotypes. Future work might opt to use the short form of the CAPQ to minimize gender-based DIF. In addition, potential biases in measures of substance use problems deserve more attention.This study aimed to genotype the polymorphism (c.654G > A) in the exon 3 of the insulin-like growth factor 1 receptor gene (IGF1R) and to analyze its association with growth, body size, slaughter and meat quality traits in Colored Polish Merino sheep. In total, 67 traits were analyzed. The IGF1R polymorphism was genotyped using the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) method. The MIXED procedure of the SAS software was used to assess the genotypic effects of the polymorphism (c.654G > A) on production traits of interest. The IGF1R c.654G > A genotypes were found to have a significant effect on the average daily gain between the 56th and 78th day of life, cold carcass, leg part, leg cut, fore shank, and kidney weights, as well as eye of loin depth, intramuscular fat content, and water-holding capacity of meat. The results suggest that the studied polymorphism may provide useful information for marker-assisted selection for increased meat performance in Colored Polish Merino sheep.The in vitro 3D model established from murine pluripotential stem cells (i.e., embryoid bodies (EBs)) is a dynamic model for endothelial differentiation. The aim of the present study was to investigate whether digital image analysis (DIA) can be applied on histological sections of EBs in order to quantify endothelial differentiation over time. The EBs were established in suspension cultures for 21 days in three independent replicate experiments. At day 4, 6, 9, 14, 18, and 21, the EBs were fixed in formaldehyde, embedded in paraffin and immunohistochemically (IHC) stained for CD31. The IHC-stained slides were digitally scanned and analysed using the Visiopharm® Quantitative Digital Pathology software Oncotopix™. The EBs developed CD31+ vascular-like structures during their differentiation. The quantitative DIA of the EBs showed that the log10 values of the relative CD31+ areas increased from -0.574 ± 0.470 (mean ± SD) at day 4 to 0.093 ± 0.688 (mean ± SD) at day 21 (p less then 0.001). The approach presented in this study is a fast, quantitative and reproducible alternative method for an otherwise time-consuming and observer-dependent histological investigation. The future perspectives for such a system would be implementation of a modified version of the method on different 3D cultures and IHC markers.Impaired brain development has been observed in newborns with congenital heart disease (CHD). We performed graph theoretical analyses and network-based statistics (NBS) to assess global brain network topology and identify subnetworks of altered connectivity in infants with CHD prior to cardiac surgery. Fifty-eight infants with critical/serious CHD prior to surgery and 116 matched healthy controls as part of the developing Human Connectome Project (dHCP) underwent MRI on a 3T system and high angular resolution diffusion MRI (HARDI) was obtained. Multi-tissue constrained spherical deconvolution, anatomically constrained probabilistic tractography (ACT) and spherical-deconvolution informed filtering of tractograms (SIFT2) was used to construct weighted structural networks. Network topology was assessed and NBS was used to identify structural connectivity differences between CHD and control groups. Structural networks were partitioned into core and peripheral nodes, and edges classed as core, peripheral, or feeder. NBS identified one subnetwork with reduced structural connectivity in CHD infants involving basal ganglia, amygdala, hippocampus, cerebellum, vermis, and temporal and parieto-occipital lobe, primarily affecting core nodes and edges. However, we did not find significantly different global network characteristics in CHD neonates. This locally affected sub-network with reduced connectivity could explain, at least in part, the neurodevelopmental impairments associated with CHD.

Multiple system atrophy (MSA) is an atypical parkinsonian syndrome and often difficult to discriminate clinically from progressive supranuclear palsy (PSP) and Parkinson’s disease (PD) in early stages. Although a characteristic metabolic brain network has been reported for MSA, it is unknown whether this network can provide a clinically useful biomarker in different centers. This study was aimed to identify and cross-validate MSA-related brain network and assess its ability for differential diagnosis and clinical correlations in Chinese and American patient cohorts.

We included

F-FDG PET scans retrospectively from 128 clinically diagnosed parkinsonian patients (34 MSA, 34 PSP and 60 PD) and 40 normal subjects in China and in the USA. Using PET images from 20 moderate-stage MSA patients of parkinsonian subtype and 20 normal subjects in both centers, we reproduced MSA-related pattern (MSAPRP) of spatial covariance and estimated its reliability. MSAPRP scores were evaluated in assessing differential diagnoluating disease discrimination and clinical correlates. This study supports differential diagnosis of MSA regardless of different patient populations, PET scanners and imaging protocols.

We have demonstrated reproducible metabolic topographies associated with MSA at both network and regional levels in two independent patient cohorts. Moreover, MSAPRP scores are sensitive for evaluating disease discrimination and clinical correlates. This study supports differential diagnosis of MSA regardless of different patient populations, PET scanners and imaging protocols.