Simulation of the ligand-leaving process of the human heat shock protein.

The human heat shock protein plays a critical role in various diseases and is an important target for pharmacological modulation. Simulation of conformational changes and free energy profiles of the human heat shock protein derived by the ligand-leaving process is a challenging issue. In this work, steered molecular dynamics simulation was adopted to simulate the ligand-leaving process. Two composite systems of heat shock protein NHSP90 and small molecules 6FJ and 6G7 are selected as research objects. The free energy during the leaving of ligand small molecules is calculated using conventional molecular dynamics simulation, steered molecular dynamics simulation (SMD), and the umbrella sampling method. We found that the a slower pulling velocity (0.001 nm ns-1) will result in 2.19 kcal mol-1, and the umbrella sampling method gives a value of 3.26 kcal mol-1 for the free energy difference for the two systems, which reasonably agrees with experimental results. A faster-pulling velocity (0.01 nm ns-1) leads to a large overestimation of free energy. At the same time, the conformational analysis indicated that the faster pulling velocity may lead to the conformational change of NHSP90, which was proved to be false by the slower pulling velocity and the umbrella sampling method.

Fetal weight estimation based on deep neural network: a retrospective observational study.

BACKGROUND: Improving the accuracy of estimated fetal weight (EFW) calculation can contribute to decision-making for obstetricians and decrease perinatal complications. This study aimed to develop a deep neural network (DNN) model for EFW based on obstetric electronic health records. METHODS: This study retrospectively analyzed the electronic health records of pregnant women with live births delivery at the obstetrics department of International Peace Maternity & Child Health Hospital between January 2016 and December 2018. The DNN model was evaluated using Hadlock's formula and multiple linear regression. RESULTS: A total of 34824 live births (23922 primiparas) from 49896 pregnant women were analyzed. The root-mean-square error of DNN model was 189.64 g (95% CI 187.95 g-191.16 g), and the mean absolute percentage error was 5.79% (95%CI: 5.70%-5.81%), significantly lower compared to Hadlock's formula (240.36 g and 6.46%, respectively). By combining with previously unreported factors, such as birth weight of prior pregnancies, a concise and effective DNN model was built based on only 10 parameters. Accuracy rate of a new model increased from 76.08% to 83.87%, with root-mean-square error of only 243.80 g. CONCLUSIONS: Proposed DNN model for EFW calculation is more accurate than previous approaches in this area and be adopted for better decision making related to fetal monitoring.

A Cu(II) MOF with laccase-like activity for colorimetric detection of 2,4-dichlorophenol and p-nitrophenol.

Metal-organic framework (MOF) materials with aqueous stability have a good potential application in the field of mimetic enzymes. However, most of them have poor robustness in aqueous solution due to competitive coordination effects between water molecules and central metal ions. Herein, a copper-based MOF (Cu-SM MOF) was prepared using copper ions and 5-(sulfomethyl) isophthalic acid (5-SMIPA) by a hydrothermal process. Considering the similarity of coordination and morphology with HKUST-1, the aqueous stability and laccase-like activity of the Cu-SM MOF were investigated using HKUST-1 as the reference. The Cu-SM MOF shows superior aqueous stability to HKUST-1 after immersion in buffer solutions, especially under alkaline conditions. Moreover, the Cu-SM MOF possesses higher catalytic activity than HKUST-1 at a high salt concentration, high temperature, etc., because the Cu-SM MOF exhibits lower Km and higher Vmax values than those of laccase and reported mimetic enzymes. The mimetic enzyme behavior of the Cu-SM MOF is demonstrated in the oxidation of phenols, as well as in the detection of 2,4-dichlorophenol (2,4-DP) and p-nitrophenol with linear ranges of 1-100 µM and 2-250 µM, and limits of detection of 0.53 µM and 1.62 µM, respectively. Owing to the excellent aqueous stability and laccase-like activity of the Cu-SM MOF, it has great application prospects in many fields, such as the determination of phenols and the treatment of industrial wastewater.

Increasing audiovisual speech integration in autism through enhanced attention to mouth.

Autistic children (AC) show less audiovisual speech integration in the McGurk task, which correlates with their reduced mouth-looking time. The present study examined whether AC's less audiovisual speech integration in the McGurk task could be increased by increasing their mouth-looking time. We recruited 4- to 8-year-old AC and nonautistic children (NAC). In two experiments, we manipulated children's mouth-looking time, measured their audiovisual speech integration by employing the McGurk effect paradigm, and tracked their eye movements. In Experiment 1, we blurred the eyes in McGurk stimuli and compared children's performances in blurred-eyes and clear-eyes conditions. In Experiment 2, we cued children's attention to either the mouth or eyes of McGurk stimuli or asked them to view the McGurk stimuli freely. We found that both blurring the speaker's eyes and cuing to the speaker's mouth increased mouth-looking time and increased audiovisual speech integration in the McGurk task in AC. In addition, we found that blurring the speaker's eyes and cuing to the speaker's mouth also increased mouth-looking time in NAC, but neither blurring the speaker's eyes nor cuing to the speaker's mouth increased their audiovisual speech integration in the McGurk task. Our findings suggest that audiovisual speech integration in the McGurk task in AC could be increased by increasing their attention to the mouth. Our findings contribute to a deeper understanding of relations between face attention and audiovisual speech integration, and provide insights for the development of professional supports to increase audiovisual speech integration in AC. HIGHLIGHTS: The present study examined whether audiovisual speech integration in the McGurk task in AC could be increased by increasing their attention to the speaker's mouth. Blurring the speaker's eyes increased mouth-looking time and audiovisual speech integration in the McGurk task in AC. Cuing to the speaker's mouth also increased mouth-looking time and audiovisual speech integration in the McGurk task in AC. Audiovisual speech integration in the McGurk task in AC could be increased by increasing their attention to the speaker's mouth.

Early development of social attention in toddlers at high familial risk for autism spectrum disorder.

The present study explored the early development of social attention of toddlers at high familial risk (HR) for autism spectrum disorder (ASD). Eighteen HR toddlers and twenty-two toddlers at low familial risk for ASD (LR) between 11 and 24 months were asked to watch paired social and non-social videos. We found that: (1) the initial social preference in HR group decreased with age, but not in LR group; (2) both groups showed significant social habituation across trials, but HR group habituated slightly slower as age increased. These findings suggest that atypical social attention could be an early characteristic of toddlers at high familial risk for ASD.

Investigating intra-individual variability of face scanning in autistic children.

LAY ABSTRACT: Atypical face scanning is suggested to be related to social interactions and communicative deficits in autistic children. We systematically examined whether autistic and non-autistic children used consistent scanning patterns when performing different tasks and scanning different types of faces. We found that autistic children scanned faces more variably than non-autistic children: While non-autistic children used more consistent scanning patterns, autistic children's scanning patterns changed frequently when watching different faces. Autistic children's variable face scanning patterns might delay and impair face processing, resulting in a social interaction deficit. What's more, variable scanning patterns may create an unstable and unpredictable perception of the environment for autistic children. Developing in such an unstable environment might motivate autistic children to retract from the environment, avoid social interaction, and focus instead on the performance of repetitive behavior. Therefore, studying face scanning variability might represent a new avenue for understanding core symptoms in autistic people.

Heterogeneity of Visual Preferences for Biological and Repetitive Movements in Children With Autism Spectrum Disorder.

Previous studies have repeatedly reported atypical visual preferences to repetitive movements and deficient perception of biological movements in individuals with autism spectrum disorder (ASD). However, limited research has investigated the heterogeneity of the visual preferences in individuals with ASD. In the current study, we explored the visual preferences to different movement types (repetitive, biological, and random) in children with ASD using a paired preferential looking paradigm. Thirty-nine children with ASD and 37 typically developing (TD) children participated in our study, with their eye movements recorded as the index of visual preferences. We examined the differences of visual preferences between the ASD and TD group, and the heterogeneity of visual preferences within the ASD group. We found group differences between children with ASD and TD children: Overall, the ASD group preferred repetitive movements while the TD group preferred biological movements. We also detected heterogeneity of visual preferences within the ASD group: Although the majority of children with ASD preferred repetitive movements as previous studies reported, 9 out of 39 children with ASD preferred biological movements similarly as their TD peers. Moreover, the visual preference patterns were correlated with autistic symptoms, especially the socio-communicative impairments. Our study provided evidence of heterogeneity of visual attention and main visual preference to repetitive movements in children with ASD. The findings add to the body of literature of the heterogeneous behavioral symptoms and the atypical visual preferences in individuals with ASD. LAY SUMMARY: The current study examined visual preferences to biological, repetitive, and random movements in children with Autism Spectrum Disorder (ASD). We showed a pair of two videos representing two types of movements (random, repetitive, or biological movements) to children with ASD and typically developing children. We found the main visual preferences for repetitive movements and heterogeneity of visual attention within the ASD group. Our findings provide theoretical and methodological implications for future study of the heterogeneity in the ASD population.

Children with Autism Spectrum Disorder Prefer Looking at Repetitive Movements in a Preferential Looking Paradigm.

The present study aimed to investigate the visual preference for repetitive movements in children with autism spectrum disorder (ASD). Young children with ASD and typically-developing (TD) children were presented simultaneously with cartoons depicting repetitive and random movements respectively, while their eye-movements were recorded. We found that: (1) the children with ASD spent more time fixating on the repetitive movements than the random movements, whereas the TD children showed no preference for either type of movements; (2) the children's preference for the repetitive movements was correlated with the parent reports of their repetitive behaviors. Our findings show a promise in using the preferential looking as a potential indicator for the repetitive behaviors and aiding early screening of ASD in future investigations.