Neural mechanisms of Chinese character recognition, updating, and maintenance in the N-back task.

Using the N-back task, we investigated how memory load influences the neural activity of the Chinese character cognitive subprocess (recognition, updating, and maintenance) in Mainland Chinese speakers. Twenty-seven participants completed the Chinese character N-back paradigm while having their event-related potentials recorded. The study employed time and frequency domain analyses of EEG data. Results showed that accuracy decreased and response times increased with larger N values. For ERPs, N2pc and P300 amplitudes decreased and SW amplitude increased with larger N values. For time frequency analyses, the desynchronization of alpha oscillations decreased after stimulus onset, but the synchronization of alpha oscillations increased during the maintenance phase. The results suggest that greater memory load is related to a decrease in cognitive resources during updating and an increase in cognitive resources during information maintenance. The results of a behavioral-ERP data structural equation model analysis showed that the ERP indicators in the maintenance phase predicted behavioral performance.

Using macromolecular electron densities to improve the enrichment of active compounds in virtual screening.

The quest for effective virtual screening algorithms is hindered by the scarcity of training data, calling for innovative approaches. This study presents the use of experimental electron density (ED) data for improving active compound enrichment in virtual screening, supported by ED's ability to reflect the time-averaged behavior of ligands and solvents in the binding pocket. Experimental ED-based grid matching score (ExptGMS) was developed to score compounds by measuring the degree of matching between their binding conformations and a series of multi-resolution experimental ED grids. The efficiency of ExptGMS was validated using both in silico tests with the Directory of Useful Decoys-Enhanced dataset and wet-lab tests on Covid-19 3CLpro-inhibitors. ExptGMS improved the active compound enrichment in top-ranked molecules by approximately 20%. Furthermore, ExptGMS identified four active inhibitors of 3CLpro, with the most effective showing an IC50 value of 1.9 µM. We also developed an online database containing experimental ED grids for over 17,000 proteins to facilitate the use of ExptGMS for academic users.

Comparison of the Aroma-Active Compounds and Sensory Characteristics of Different Grades of Light-Flavor Baijiu.

This study comprehensively characterized and compared the aroma differences between four different grades of Fenjiu (FJ, the most representative light-flavor Baijiu). Aroma-active compounds were analyzed by liquid-liquid extraction (LLE) coupled with gas chromatography-olfactometry-mass spectrometry (GC-O-MS). A total of 88 aroma-active compounds were identified, and 70 of them were quantified. The results showed that a majority of aroma compounds in high-grade FJ had higher aroma intensities and concentrations. Among these compounds, there were 28 compounds with odor activity values (OAVs) greater than one in all four wines, which indicated that they might contribute to the characteristic aroma of FJ. Temporal dominance of sensation (TDS) and quantitative descriptive analysis (QDA) were used to characterize the sensory differences. The results suggested that high-grade FJ had a rich, pleasant and lasting retronasal aroma perception and exhibited pleasant orthonasal aroma of floral, fruity, sweet and grassy. Partial least squares regression (PLSR) analysis effectively distinguished four kinds of FJ and revealed associations between the orthonasal aroma attributes and the aroma compounds with OAVs >1. There were 15 compounds with variable importance in projection (VIP) values >1, and they were considered potential aroma markers for quality prediction.

A pocket-based 3D molecule generative model fueled by experimental electron density.

We report for the first time the use of experimental electron density (ED) as training data for the generation of drug-like three-dimensional molecules based on the structure of a target protein pocket. Similar to a structural biologist building molecules based on their ED, our model functions with two main components: a generative adversarial network (GAN) to generate the ligand ED in the input pocket and an ED interpretation module for molecule generation. The model was tested on three targets: a kinase (hematopoietic progenitor kinase 1), protease (SARS-CoV-2 main protease), and nuclear receptor (vitamin D receptor), and evaluated with a reference dataset composed of over 8000 compounds that have their activities reported in the literature. The evaluation considered the chemical validity, chemical space distribution-based diversity, and similarity with reference active compounds concerning the molecular structure and pocket-binding mode. Our model can generate molecules with similar structures to classical active compounds and novel compounds sharing similar binding modes with active compounds, making it a promising tool for library generation supporting high-throughput virtual screening. The ligand ED generated can also be used to support fragment-based drug design. Our model is available as an online service to academic users via https://edmg.stonewise.cn/#/create .

Hope as a Process in Understanding Positive Mood and Suicide Protection.

Background: According to the broaden-and-build model of positive mood, positive emotions are believed to broaden cognition resources and build psychological resiliency, to help incur positive psychological outcomes. Aim: We examined hope as a potential mediator of the association between positive mood and suicide protection (viz., life satisfaction and reasons for living) in adults. We hypothesized that positive mood would be associated with greater suicide protection through broadening hope agency and building hope pathways. Method: A sample of 320 college students completed measures of positive emotions, hope, and suicide protection. Results: Results from bootstrapped mediation testing indicated that hope agency, but not hope pathways, partially or fully mediated the relationship between positive mood and suicide protection. Limitations: It is not clear whether these findings are generalizable to a more diverse adult population. Also, it is not possible to rule out alternative causal models involving positive emotions and suicide protection. Conclusion: These findings provide some promising preliminary evidence for how positive emotions might help build hope agency to foster greater suicide protection in adults.

Studies of Conformational Changes of Tubulin Induced by Interaction with Kinesin Using Atomistic Molecular Dynamics Simulations.

The transition between strong and weak interactions of the kinesin head with the microtubule, which is regulated by the change of the nucleotide state of the head, is indispensable for the processive motion of the kinesin molecular motor on the microtubule. Here, using all-atom molecular dynamics simulations, the interactions between the kinesin head and tubulin are studied on the basis of the available high-resolution structural data. We found that the strong interaction can induce rapid large conformational changes of the tubulin, whereas the weak interaction cannot. Furthermore, we found that the large conformational changes of the tubulin have a significant effect on the interaction of the tubulin with the head in the weak-microtubule-binding ADP state. The calculated binding energy of the ADP-bound head to the tubulin with the large conformational changes is only about half that of the tubulin without the conformational changes.

The Effect of Solution-Focused Group Counseling Intervention on College Students' Internet Addiction: A Pilot Study.

This pilot study aimed to explore the effect of solution-focused group counseling intervention on Internet addiction among college students. Eighteen college students participated in this study, out of which nine subjects were assigned into the experimental group and the rest (n = 9) to a control group. The experimental group received group counseling for five weeks, while the control group did not receive any intervention. The revised version of the Chinese Internet Addiction Scale (CIAS-R) was used to capture pre-test and post-test excessive use in the two groups. The experimental group was also subjected to a follow-up test and self-reported Internet addiction scores six months after the end of group counseling. Results showed that after the five-week solution-focused group counseling, the scores of four dimensions of the CIAS-R in the experimental group had CIAS-R decreased, and the reduction trend of the total score of CIAS-R was similar across all subjects in this group. The treatment effect was larger than the placebo reduction in the control group in two dimensions: compulsive and withdrawal (Sym-C & Sym-W) and tolerance (Sym-T) symptoms. Qualitative research confirmed the conclusions from the quantitative data, showing that the experimental group reduced its Internet addiction symptoms. Overall, the findings suggested that solution-focused group counseling had positive intervention effects on Internet addiction.

Secure attachments predict prosocial behaviors: A moderated mediation study.

Previous research has shown that secure attachment promotes prosocial behavior. However, the mechanism underlying the link between attachment and prosocial behavior has received relatively little attention. The current study examined the mechanism underlying the link between attachment and prosocial behavior by specifically focusing on the potential mediating role of moral disengagement and whether this mediation effect is moderated by moral identity. Self-report questionnaires designed to measure attachment, moral identity, moral disengagement, and prosocial behavior were administered to Chinese students (n = 395; 250 females; Mage = 23.38 years). Results showed that secure attachment (maternal attachment, paternal attachment, and peer attachment) was associated with prosocial behavior. In addition, moral disengagement was found to mediate the association between secure attachment and prosocial behavior. Moreover, the mediation effect was moderated by moral identity; specifically, the mediation effect was stronger for individuals with a high level of moral identity than their low-level moral identity counterparts. The present results suggest that morality could explain the association between attachment and prosocial behaviors.

Boosting attachment security to cope with threats: Behavioral and ERPs findings.

Attachment security describes a sense of safety and security felt by individuals and promotes mental health. The mechanism by which attachment security buffers against psychological threat remains unclear, however. Here, we explored how attachment security attenuates the response to threatening information using a signal detection theory (SDT) and event-related potentials (ERPs) approach. Participants were assigned to an attachment security priming condition or a control condition. After a priming procedure, behavioral data and electroencephalography (EEG) signals were recorded while participants categorized threatening and neutral pictures. Our behavioral results revealed that attachment security biased participant responses to categorizing the two types of pictures; participants in the control condition exhibited a tendency to categorize stimuli as threatening, whereas those in the attachment security condition tended to categorize stimuli as neutral. Meanwhile, attachment security priming modulated early attention processes, reflected by an increased P200. The findings reported here suggest that attachment security buffers against external threats by modulating individual response preferences, the effects of which manifest in the early stages of attentional processing.

All-atom molecular dynamics simulations reveal how kinesin transits from one-head-bound to two-heads-bound state.

Kinesin dimer walks processively along a microtubule (MT) protofilament in a hand-over-hand manner, transiting alternately between one-head-bound (1HB) and two-heads-bound (2HB) states. In 1HB state, one head bound by adenosine diphosphate (ADP) is detached from MT and the other head is bound to MT. Here, using all-atom molecular dynamics simulations we determined the position and orientation of the detached ADP-head relative to the MT-bound head in 1HB state. We showed that in 1HB state when the MT-bound head is in ADP or nucleotide-free state, with its neck linker being undocked, the detached ADP-head and the MT-bound head have the high binding energy, and after adenosine triphosphate (ATP) binds to the MT-bound head, with its neck linker being docked, the binding energy between the two heads is reduced greatly. These results reveal how the kinesin dimer retains 1HB state before ATP binding and how the dimer transits from 1HB to 2HB state after ATP binding. Key residues involved in the head-head interaction in 1HB state were identified.

Run length distribution of dimerized kinesin-3 molecular motors: comparison with dimeric kinesin-1.

Kinesin-3 and kinesin-1 molecular motors are two families of the kinesin superfamily. It has been experimentally revealed that in monomeric state kinesin-3 is inactive in motility and cargo-mediated dimerization results in superprocessive motion, with an average run length being more than 10-fold longer than that of kinesin-1. In contrast to kinesin-1 showing normally single-exponential distribution of run lengths, dimerized kinesin-3 shows puzzlingly Gaussian distribution of run lengths. Here, based on our proposed model, we studied computationally the dynamics of kinesin-3 and compared with that of kinesin-1, explaining quantitatively the available experimental data and revealing the origin of superprocessivity and Gaussian run length distribution of kinesin-3. Moreover, predicted results are provided on ATP-concentration dependence of run length distribution and force dependence of mean run length and dissociation rate of kinesin-3.

Force dependence of unbinding rate of kinesin motor during its processive movement on microtubule.

Kinesin is a biological molecular motor that can move continuously on microtubule until it unbinds. Here, we studied computationally the force dependence of the unbinding rate of the motor. Our results showed that while the unbinding rate under the forward load has the expected characteristic of "slip bond", with the unbinding rate increasing monotonically with the increase of the forward load, the unbinding rate under the backward load shows counterintuitive characteristic of "slip-catch-slip bond": as the backward load increases, the unbinding rate increases exponentially firstly, then drops rapidly and then increases again. Our calculated data are in agreement with the available single-molecule data from different research groups. The mechanism of the slip-catch-slip bond was revealed.

Dynamics of tRNA dissociation in early and later cycles of translation elongation by the ribosome.

Deacylated tRNA dissociation from E site and aminoacyl-tRNA binding to the A site of the ribosome play a critical role in repetitive cycles of protein synthesis. Available experimental data showed that in the small range of aminoacyl-tRNA concentrations, during the first few cycles of translation elongation (initiation phase of translation) the E-site tRNA can be dissociated either before or after the A-site tRNA binding, while during the later cycles of elongation (elongation phase) the E-site tRNA is mostly dissociated before the A-site tRNA binding. Here, based on our proposed model of translation elongation we study analytically the dynamics of the E-site tRNA dissociation and A-site tRNA binding, providing quantitative explanations of the available experimental data in both the initiation and elongation phases. In our model there exist two routes of state transitions within an elongation cycle in the initiation phase, with each route having stochastic E-site tRNA dissociation but with different dissociation rates. Thus, the E-site tRNA dissociation is governed by a stochastic competition between the tRNA dissociation and A-site tRNA association reactions, although in the small range of aminoacyl-tRNA concentrations used in the experiments it seems that such stochastic competition does not exist. Moreover, the detailed comparisons between the dynamics of tRNA dissociation in the initiation phase and that in the elongation phase are made.

Processivity of dimeric kinesin-1 molecular motors.

Kinesin-1 is a homodimeric motor protein that can move along microtubule filaments by hydrolyzing ATP with a high processivity. How the two motor domains are coordinated to achieve such high processivity is not clear. To address this issue, we computationally studied the run length of the dimer with our proposed model. The computational data quantitatively reproduced the puzzling experimental data, including the dramatically asymmetric character of the run length with respect to the direction of external load acting on the coiled-coil stalk, the enhancement of the run length by addition of phosphate, and the contrary features of the run length for different types of kinesin-1 with extensions of their neck linkers compared with those without extension of the neck linker. The computational data on other aspects of the movement dynamics such as velocity and durations of one-head-bound and two-head-bound states in a mechanochemical coupling cycle were also in quantitative agreement with the available experimental data. Moreover, predicted results are provided on dependence of the run length upon external load acting on one head of the dimer, which can be easily tested in the future using single-molecule optical trapping assays.

Investigating role of conformational changes of microtubule in regulating its binding affinity to kinesin by all-atom molecular dynamics simulation.

Changes of affinity of kinesin head to microtubule regulated by changes in the nucleotide state are essential to processive movement of kinesin on microtubule. Here, using all-atom molecular dynamics simulations we show that besides the nucleotide state, large conformational changes of microtubule-tubulin heterodimers induced by strong interaction with the head in strongly binding state are also indispensable to regulate the affinity of the head to the tubulin. In strongly binding state the high affinity of the head to microtubule arises largely from mutual conformational changes of the microtubule and head induced by the specific interaction between them via an induced-fit mechanism. Moreover, the ADP-head has a much weaker affinity to the local microtubule-tubulin, whose conformation is largely altered by the interaction with the head in strongly binding state, than to other unperturbed tubulins. This indicates that upon Pi release the ADP-head temporarily has a much weaker affinity to the local tubulin than to other tubulins.

Fast photocatalytic degradation of methylene blue dye using a low-power diode laser.

This study focused on the application of diode lasers as alternative light sources for the fast photocatalytic degradation of methylene blue. The photocatalytic decomposition of methylene blue in aqueous solution under 443 nm laser light irradiation was found to be technically feasible using Ag/AgCl nanoparticles as photocatalysts. The effects of various experimental parameters, such as irradiation time, light source, catalyst loading, initial dye concentration, pH, and laser energy on decolorization and degradation were investigated. The mineralization of methylene blue was confirmed by chemical oxygen demand analysis. The results demonstrate that the laser-induced photocatalytic process can effectively degrade methylene blue under the optimum conditions (pH 9.63, 4 mg/L MB concentration, and 1.4 g/L Ag/AgCl nanoparticles).