GENERALIST: A latent space based generative model for protein sequence families.

Generative models of protein sequence families are an important tool in the repertoire of protein scientists and engineers alike. However, state-of-the-art generative approaches face inference, accuracy, and overfitting- related obstacles when modeling moderately sized to large proteins and/or protein families with low sequence coverage. Here, we present a simple to learn, tunable, and accurate generative model, GENERALIST: GENERAtive nonLInear tenSor-factorizaTion for protein sequences. GENERALIST accurately captures several high order summary statistics of amino acid covariation. GENERALIST also predicts conservative local optimal sequences which are likely to fold in stable 3D structure. Importantly, unlike current methods, the density of sequences in GENERALIST-modeled sequence ensembles closely resembles the corresponding natural ensembles. Finally, GENERALIST embeds protein sequences in an informative latent space. GENERALIST will be an important tool to study protein sequence variability.

SiGMoiD: A super-statistical generative model for binary data.

In modern computational biology, there is great interest in building probabilistic models to describe collections of a large number of co-varying binary variables. However, current approaches to build generative models rely on modelers' identification of constraints and are computationally expensive to infer when the number of variables is large (N~100). Here, we address both these issues with Super-statistical Generative Model for binary Data (SiGMoiD). SiGMoiD is a maximum entropy-based framework where we imagine the data as arising from super-statistical system; individual binary variables in a given sample are coupled to the same 'bath' whose intensive variables vary from sample to sample. Importantly, unlike standard maximum entropy approaches where modeler specifies the constraints, the SiGMoiD algorithm infers them directly from the data. Due to this optimal choice of constraints, SiGMoiD allows us to model collections of a very large number (N>1000) of binary variables. Finally, SiGMoiD offers a reduced dimensional description of the data, allowing us to identify clusters of similar data points as well as binary variables. We illustrate the versatility of SiGMoiD using multiple datasets spanning several time- and length-scales.

Prevalence and risks of mild cognitive impairment of Chinese community-dwelling women aged above 60 years: A cross-sectional study.

Evidence has shown that risks of cognitive impairment differ between genders. This cross-sectional study sought to determine the prevalence of mild cognitive impairment (MCI) in Chinese community-dwelling women aged above 60 years and identify risks of MCI by multivariate logistic regression analysis. Totally, 1760 Chinese community-dwelling women entered the study. Cognitive function was assessed with Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). MCI was diagnosed by Petersen's criteria. Sociodemographic information, past medical conditions, and age at menopause were screened. The primary study outcome was prevalence of MCI. MCI was diagnosed in 378 (21.5%) women. Older age was a significant risk of MCI (OR 1.621, 95%CI 1.386-1.894; P < 0.001). Low education was associated a 4-fold increase in the risk of MCI (OR 4.036, 95%CI 3.168-5.142). Furthermore, current depression was associated with 2.6-fold increase in the risk of MCI (OR 2.618, 95%CI 1.499-4.587, P = 0.001). Moreover, frequent physical exercise and more leisure and social time activities were associated with significantly reduced risks of MCI, while poor financial status was associated with a significantly increased risk of MCI. Slightly more than 20% of Chinese women aged above 60 years had MCI, and independent risks included older age, low education status, and current depression, highlighting the importance of screening for and removing or minimizing risks of MCI in this specific population.

H-NS uses an autoinhibitory conformational switch for environment-controlled gene silencing.

As an environment-dependent pleiotropic gene regulator in Gram-negative bacteria, the H-NS protein is crucial for adaptation and toxicity control of human pathogens such as Salmonella, Vibrio cholerae or enterohaemorrhagic Escherichia coli. Changes in temperature affect the capacity of H-NS to form multimers that condense DNA and restrict gene expression. However, the molecular mechanism through which H-NS senses temperature and other physiochemical parameters remains unclear and controversial. Combining structural, biophysical and computational analyses, we show that human body temperature promotes unfolding of the central dimerization domain, breaking up H-NS multimers. This unfolding event enables an autoinhibitory compact H-NS conformation that blocks DNA binding. Our integrative approach provides the molecular basis for H-NS-mediated environment-sensing and may open new avenues for the control of pathogenic multi-drug resistant bacteria.

Functional deficit of sense organs as a risk factor for cognitive functional disorder in Chinese community elderly people.

OBJECTIVE: To explore the relationship between mild cognitive impairment (MCI) and sense organs functional deficit in community elderly people. METHODS: A total of 3095 community elderly people above 60 years in Hebei Province were selected by cross-sectional random cluster sampling method, who were evaluated face-to-face for general demographic data, the condition of sense organs functional deficit (vision, hearing, gustation, olfactory sensation, taste) and cognitive function by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). RESULTS: A total of 3075 valid questionnaires were obtained. (a) 1368 old people (44.49%) were defined with sense organs functional deficit (defined as one or more of glaucoma, fundus disease, hearing impairment, olfactory disorder and taste disorder) in 3095 elderly people. According to questionnaires, MCI was diagnosed in 689 of 3075 participants (22.41%). The hearing disorder and glaucoma of MCI group were higher than that of the normal control group (X2 were 5.998 and 7.430, respectively, P were .014 and .006, respectively). (b) The MMSE score of the hearing disorder were significantly lower than those of non-hearing disorder group (t = 2.046, P = .041). (c) Multinomial logistics regression analysis was applied by MCI as the dependent variable and the various sensory organs defects as independent variables. The hearing impairment (Wald = 8.582, P = .003, OR = 1.485, 95% CI: 1.140-1.934) and glaucoma (Wald = 8.020, P = .005, OR = 1.847, 95% CI: 1.208-2.824) were associated with MCI. CONCLUSION: The sensory organs functional defects is associated with the mild cognitive impartment in Chinese elderly, especially in vision and hearing disorder.

Experiencing earthquake in the first trimester of the fetal life increases subsequent diabetes risk in the adulthood: a cross-sectional study.

OBJECTIVE: To investigate the long-term effect of prenatal exposure to earthquake stress on diabetes risk in the adulthood. METHODS: This study included employees of Tangshan Kailuan Mining Group between July 29, 1976 and April 28, 1977. The exposure group included subjects who experienced the Tangshan Earthquake during their prenatal period and who had lived in Tangshan since birth. The non-exposure group included subjects who were born 1-1.9 years after the earthquake and who had lived in Tangshan since birth. A questionnaire was designed that included sociodemographic information, conditions during pregnancy, and earthquake experience. Anthropometric measurements including height and weight, body mass index (BMI), waist circumference were made. Fasting plasma glucose (FPG) and lipid profiles were also determined. RESULTS: Totally 947 subjects were included with 397 subjects in the exposed group and 550 subjects in the non-exposed group. The diabetes rate is significant different in these four groups(χ2 =8.045, P = 0.045). Moreover, 11.8, 7.5 and 8.0% of the subjects who were exposed to earthquake in the 1st, 2nd, and 3rd trimester of pregnancy had diabetes. 5.1% of the subjects had diabetes in non-exposure group. Our multivariate analysis showed that 1st trimester (OR 2.481, 95%CI 1.02, 6.034; P = 0.045) and loss of family members during earthquake (OR 2.452, 95%CI 1.293, 4.653; P = 0.006) were associated with significantly increased risk of diabetes. CONCLUSIONS: Exposure to earthquake during the first trimester of pregnancy and experience of family member loss in the earthquake significantly increased the subsequent risk of diabetes in the middle age (36-39 years of age). Our data suggest that earthquake experience in the early pregnancy has a longer-term effect on diabetes risk during adulthood.

Evaluation of childhood traumatic experience as a risk factor for alcohol use disorder in adulthood.

BACKGROUND: We aimed to investigate the effect of early-age (prenatal, infant, and childhood) trauma on adulthood alcohol use disorder. METHODS: A total number of 1534 subjects who were born and live in the city of Tangshan were selected. The subjects were divided into three age groups. General demographic data, conditions of the mothers during pregnancy, and condition of the babies at birth, were collected. The diagnosis of alcohol use disorder was based on Structured Clinical Interviews for DSM-IV Axis Disorders (patient version) (SCID). The childhood trauma questionnaire short form (CTQ-SF) [1] and the Lifetime of Experience Questionnaire (LTE-Q) [2] were used to evaluate stress in childhood and adulthood, respectively. RESULTS: Only male subjects were diagnosed with lifelong alcohol abuse and alcohol dependence. There was no statistically significant difference in the prevalence of lifetime alcohol use disorder (X2 = 4.480, P = 0.345), current alcohol abuse, and current alcohol dependence among the three groups (X2abuse = 2.177, X2depedence = 2.198, P > 0.05). However, higher prevalence of lifetime alcohol use disorders was found in group with higher scores of CTQ (X2 = 9.315, P = 0.009), emotional abuse (X2 = 8.025, P = 0.018), physical abuse (X2 = 20.4080, P < 0.001), but not in the group with higher scores of emotional neglect (X2 = 1.226, P = 0.542), sexual abuse (X2 = 2.779, P = 0.249), physical neglect (X2 = 3.978, P = 0.137), LTE-Q (X2 = 5.415, P = 0.067), and PSQI (X2 = 5.238, P = 0.073). Protective factor for alcohol abuse for men was identified to be heavy drinking (OR = 0.085, 95%CI: 0.011-0.661), and the risk factors for alcohol abuse were identified to be frequent drinking (OR = 2.736, 95%CI: 1.500, 4.988), and consumption of low liquor (OR = 2.563, 95%CI: 1.387, 4.734). Risk factors for alcohol dependence in males were identified to be consumption of low liquor (OR = 5.501, 95%CI: 2.004, 15.103), frequent drinking (OR = 2.680, 95%CI: 1.164, 6.170), and childhood physical abuse (OR = 2.310, 95% CI: 1.026, 5.201). CONCLUSION: Traumatic experience during infant and prenatal periods does not have a strong statistical correlation with alcohol use disorders for male adults. However, subjects with high CTQ scores, experience of emotional abuse and physical abuse show a statistically higher prevalence of lifetime alcohol use disorders. Several risk factors including consumption of low liquor, frequent drinking, and childhood physical abuse contribute to alcohol dependence in male adults.

Capturing the multiscale dynamics of membrane protein complexes with all-atom, mixed-resolution, and coarse-grained models.

The structures and dynamics of protein complexes are often challenging to model in heterogeneous environments such as biological membranes. Herein, we meet this fundamental challenge at attainable cost with all-atom, mixed-resolution, and coarse-grained models of vital membrane proteins. We systematically simulated five complex models formed by two distinct G protein-coupled receptors (GPCRs) in the lipid-bilayer membrane on the ns-to-µs timescales. These models, which suggest the swinging motion of an intracellular loop, for the first time, provide the molecular details for the regulatory role of such a loop. For the models at different resolutions, we observed consistent structural stability but various levels of speed-ups in protein dynamics. The mixed-resolution and coarse-grained models show two and four times faster protein diffusion than the all-atom models, in addition to a 4- and 400-fold speed-up in the simulation performance. Furthermore, by elucidating the strengths and challenges of combining all-atom models with reduced resolution models, this study can serve as a guide to simulating other complex systems in heterogeneous environments efficiently.

High prevalence of mild cognitive impairment in the elderly: a community-based study in four cities of the Hebei province, china.

BACKGROUND: Mild cognitive impairment (MCI) has been suggested as a term for a boundary area between normal aging and dementia. This study was designed to determine the prevalence of MCI in the elderly in the Hebei province, China, and explore its related factors. METHODS: Participants included 2,601 community-dwelling people aged 60 years or older who resided in the four major cities of the Hebei province. In stage 1 of the study, the Mini-Mental State Examination and the Montreal Cognitive Assessment were administered for screening purposes. In stage 2, the subjects who screened positive were further examined by neurologists. The diagnosis of MCI was made according to Petersen's criteria. RESULTS: The estimated prevalence of MCI was 21.3%. MCI was more prevalent at age 65-69 (28.3%), and its overall rates among men (24.1%) were higher than those of women (19.9%). The higher prevalence of MCI was associated with very old age (≥80 years old; OR = 2.457, 95% CI = 1.471-4.104), male gender (OR = 1.363, 95% CI = 1.097-1.694), low education level (OR = 2.439, 95% CI = 1.623-3.663), and poor economic status (OR = 2.882, 95% CI = 1.949-4.255). CONCLUSIONS: Our findings show a high prevalence of MCI in the elderly urban population in the Hebei province. Gender, education level, and economic status may have an important role in the etiology of MCI.

Evaluation of Essential Dynamics and Fixed-Length Coarse Graining for Multidomain Proteins.

For multiscale modeling of biomolecules, reliable coarse-grained (CG) models can offer great potential to simulate larger temporal and spatial scales than traditional all-atom (AA) models. In this study, we explore the essential dynamics coarse graining (EDCG) and fixed-length coarse graining (FLCG) approaches for constructing highly coarse-grained models for multidomain proteins (MDPs), with 1 to 10 amino acid residues per CG site. In the studies of 13 MDPs, our data indicate that both EDCG and FLCG can preserve the protein dynamics of MDPs. FLCG, which restricts an equal number of residues in each CG site, represents an excellent approximation to EDCG and a straightforward approach for coarse-graining MDPs. Furthermore, FLCG is tested with a class B G-protein-coupled receptor protein, and the agreement with prior experiments suggests its general application to various MDPs in different environments or conditions. Finally, we demonstrate another application of FLCG through progressive backmapping, showcasing the ability to recover from lower-resolution CG models (6 residues/CG site) to higher-resolution ones (1 residue/CG site). These promising outcomes underscore the broad applicability of FLCG to construct highly or ultra-coarse-grained models of complex biomolecules for multiscale simulations.

Suicidal ideation in medical students of Hebei province: prevalence and associated factors.

Objectives: This study investigated the prevalence of suicidal ideation (SI) among Chinese medical students and its associated risk factors. Methods: A total of 6643 medical students (2383 males/4260 females) were recruited from a medical college in Hebei Province, China. Demographic data were collected via a self-administered questionnaire. The Childhood Trauma Questionnaire Short Form (CTQ-SF) was used to evaluate childhood maltreatment (CM), and the Adolescent Self-Rating Life Events Checklist (ASLEC) was used to evaluate the stressful life events. Suicidal ideation was assessed using the Beck Scale for Suicide Ideation (BSSI). Univariate and multivariate logistic regression models were used to analyze the factors affecting SI. Results: The prevalence of SI in medical students was 11.5% (763/6643). Multivariate logistic regression analysis revealed that SI was significantly associated with younger age, a female sex, being lovelorn, being introverted, experiencing CM during childhood, and experiencing stressful life events within the past 12 months. Of the five subtypes of CM, emotional abuse may have the strongest effect on SI (OR=2.76, 95% CI: 1.72-4.42). The joint effects of CM and stressful life events were significantly associated with an increased risk of SI (OR=5.39, 95% CI: 4.15-6.98). Conclusion: The prevalence of SI among medical students is high, and medical students who have experienced CM and stressful life events have a higher tendency towards SI. Screening for both CM and stressful life events may be an effective way of identifying individuals at high risk of SI.

Exploring EEG characteristics of multi-level mental stress based on human-machine system.

Objective.The understanding of cognitive states is important for the development of human-machine systems (HMSs), and one of the fundamental but challenging issues is the understanding and assessment of the operator's mental stress state in real task scenarios.Approach.In this paper, a virtual unmanned vehicle (UAV) driving task with multi-challenge-level was created to explore the operator's mental stress, and the human brain activity during the task was tracked in real time via electroencephalography (EEG). A mental stress analysis dataset for the virtual UAV task was then developed and used to explore the neural activation patterns associated with mental stress activity. Finally, a multiple attention-based convolutional neural network (MACN) was constructed for automatic stress assessment using the extracted stress-sensitive neural activation features.Main Results.The statistical results of EEG power spectral density (PSD) showed that frontal theta-PSD decreased with increasing task difficulty, and central beta-PSD increased with increasing task difficulty, indicating that neural patterns showed different trends under different levels of mental stress. The performance of the proposed MACN was evaluated based on the dimensional model, and results showed that average three-class classification accuracies of 89.49%/89.88% were respectively achieved for arousal/valence.Significance.The results of this paper suggest that objective assessment of mental stress in a HMS based on a virtual UAV scenario is feasible, and the proposed method provides a promising solution for cognitive computing and applications in human-machine tasks.

Effect of hyperbaric oxygen on post-stroke depression.

BACKGROUND: In patients with post-stroke depression (PSD) in diabetes, the situation may be more complex, requiring simultaneous treatment of blood glucose, depressive symptoms, and neurological dysfunction. Hyperbaric oxygen (HBO) therapy can improve tissue oxygen content and improve the situation of ischemia and hypoxia, thus playing a role in protecting brain cells and restoring the function of brain cells. However, there are few studies on HBO therapy for patients with PSD. This study explores the clinical efficacy of such therapy for stroke complicated with depression and diabetes mellitus, and to provide reference and basis for clinical treatment and development through the application of relevant rating scales and laboratory test indicators. AIM: To evaluate the clinical effects of HBO therapy on patients with diabetes with PSD. METHODS: A total of 190 diabetic patients with PSD were randomly divided into observation and control groups (95 patients per group). The control group received escitalopram oxalate 10mg once a day for eight weeks. In addition, the ob-servation group was also given HBO therapy, once a day, five times a week, for eight weeks. The Montgomery Depression Rating Scale (MADRS), National Institutes of Health Stroke Scale (NIHSS), hypersensitive C-reactive protein, tumor necrosis factor (TNF)-α, and fasting glucose levels were compared. RESULTS: There were no significant differences in age, sex, or depression course between the groups (P > 0.05). After HBO treatment, MADRS scores in both groups decreased significantly (14.3 ± 5.2), and were significantly lower in the control group (18.1 ± 3.5). After HBO treatment, NIHSS scores in both groups decreased significantly, and scores in the observation group (12.2 ± 4.0) decreased more than in the control group (16.1 ± 3.4), the difference was statistically significant (P < 0.001). The levels of hypersensitive C-reactive protein and TNF-α in both groups were significantly decreased, and the observation group was significantly lower than the control group (P < 0.001). Fasting blood glucose levels in both groups decreased significantly, and those in the observation group decreased more (8.02 ± 1.10) than in the control group (9.26 ± 1.04), with statistical significance (t = -7.994, P < 0.001). CONCLUSION: HBO therapy can significantly improve depressive symptoms and neurological dysfunction in patients with PSD, and reduce the levels of hypersensitive C-reactive protein, TNF-α and fasting blood glucose.

Effect of night shift work on metabolic syndrome in adults who suffered from earthquake stress in early life.

Objective: To examine the role of night shift work on the risk of metabolic syndrome (MetS) in adults suffered from earthquakes prenatally or as infants and to analyse the effect of stress on factors that influence MetS in this population. Methods: We included 870 subjects from 2014 to 2015. All subjects work as miners for the Kailuan Mining Group and were born were living in Tangshan. Participants were classified into two groups on basis of their work schedules: day shift and night shift. They were further classified into the prenatal exposure group, the infancy exposure group, and the control group based on their age during the Tangshan earthquake. This study was conducted 38 years after the earthquake. Participants' general demographic data, smoking and drinking habits, as well as work schedules were collected. All participants' sleep status was assessed with the Pittsburgh Sleep Quality Index. The measurement of all subjects' waist circumference and blood pressure was made, and triglycerides, fasting blood glucose, high-density lipoproteins, and low-density lipoproteins were measured by collecting blood samples. The definition of MetS was made after the guidelines for preventing and controlling type 2 diabetes in China (2017 Edition). Results: A total of 187 (21.5%) workers were determined to have MetS. The incidence of MetS was greatly higher in night shift workers who were exposed to an earthquake during infancy than in day shift workers (χ2 = 8.053, p = 0.005). A multivariate logistic regression analysis displayed male participants had a higher risk develop MetS than female participants (p = 0.042, OR = 0.368, 95% CI = 0.140, 0.965). Current smokers (p = 0.030, OR = 1.520, 95%CI = 1.042, 2.218) and participants who sleep fewer than 7 h per night (p = 0.015, OR = 1.638, 95%CI = 1.101, 2.437) had a higher risk of MetS. Prenatal earthquake stress was also a risk element for MetS (p = 0.012, OR = 1.644, 95%CI = 1.115, 2.423). Conclusion: The risk of MetS is significantly higher in night shift workers exposed to earthquake stress during infancy than day shift workers. Earthquake exposure during pregnancy is an independent risk factor for MetS. Smoking and sleeping less than 7 h have a higher risk of MetS than the control group.

Efficiency of the Brain Network Is Associated with the Mental Workload with Developed Mental Schema.

The study of mental workload has attracted much interest in neuroergonomics, a frontier field of research. However, there appears no consensus on how to measure mental workload effectively because the mental workload is not only regulated by task difficulty but also affected by individual skill level reflected as mental schema. In this study, we investigated the alterations in the functional brain network induced by a 10-day simulated piloting task with different difficulty levels. Topological features quantifying global and local information communication and network organization were analyzed. It was found that during different tests, the global efficiency did not change, but the gravity center of the local efficiency of the network moved from the frontal to the posterior area; the small-worldness of the functional brain network became stronger. These results demonstrate the reconfiguration of the brain network during the development of mental schema. Furthermore, for the first two tests, the global and local efficiency did not have a consistent change trend under different difficulty levels, but after forming the developed mental schema, both of them decreased with the increase in task difficulty, showing sensitivity to the increase in mental workload. Our results demonstrate brain network reconfiguration during the motor learning process and reveal the importance of the developed mental schema for the accurate assessment of mental workload. We concluded that the efficiency of the brain network was associated with mental workload with developed mental schema.

Long-term effects of early stress due to earthquake exposure on depression symptoms in adulthood: a cross-sectional study.

OBJECTIVE: This study aimed to investigate the long-term effects of early stress by Tangshan earthquake on symptoms of depression in adulthood. METHOD: A total of 1534 volunteers born and raised in Tangshan were investigated; finally, 1328 subjects were enrolled in the study. They were divided into three groups according to their birth dates: infant exposure, prenatal exposure, and non-exposure. The questionnaires and psychological evaluation of all subjects were completed using a one-on-one psychological test. RESULTS: The rate of depressive symptoms in the prenatal exposure group was the highest, and the lowest in the non-exposure group, with statistical differences among the three groups (P = 0.002). Moreover, the incidences of depressed mood, suicide ideation and work and loss of interest in the prenatal exposure group were significantly higher than those in the infant exposure group and the non-exposure group (P = 0.008, P = 0.001, P = 0.038, respectively). Multiple logistic regression analysis showed that male could be a protective factor for symptoms of depression in adulthood, and earthquake exposure was an important predictor of the incidence of depression symptoms. CONCLUSIONS: Fetal or infancy exposure to earthquake might correlate to depression symptoms in adulthood.

Cortical theta-gamma coupling tracks the mental workload as an indicator of mental schema development during simulated quadrotor UAV operation.

Objective. In the emerging field of neuroergonomics, mental workload assessment is one of the most important problems. Previous studies have made some progress on the relationship between task difficulties and mental workload, but how the mental schema, a reflection of the understanding and mastery degree of a task, affects mental workload has not been clearly discussed.Approach. There is emerging appreciation for the role of theta-gamma coupling (TGC) in high-level cognitive functions. Here, we attempt to further our understanding of how mental schema development and task difficulty had an impact on mental workload from the perspective of TGC. Specifically, the variation of TGC coupling strength and coupling pattern was estimated with different test orders and task difficulties performed by 51 students in a ten-day simulated quadrotor unmanned aerial vehicle flight training and test tasks.Main results. During the training, TGC increased with mental schema development. For the test tasks, TGC did not change with increasing task difficulty before the operator formed a mental schema but decreased with the increasing mental workload after the formation of the mental schema.Significance. Our results suggest that TGC was a robust indicator of mental schema development and could be biased by task difficulty. In conclusion, TGC can be a promising measure of mental workload, but only for experienced operators.

The effect of mental schema evolution on mental workload measurement: an EEG study with simulated quadrotor UAV operation.

Objective. Mental workload is the result of the interactions between the demands of an operation task, the environment in which the task is performed, and the skills, behavior and perception of the performer. Working under a high mental workload can significantly affect an operator's ability to choose optimal decisions, judgments and motor actions while operating an unmanned aerial vehicle (UAV). However, the effect of mental schema, which reflects the level of expertise of an operator, on mental workload remains unclear. Here, we propose a theoretical framework for describing how the evolution of mental schema affects mental workload from the perspective of cognitive processing.Approach. We recruited 51 students to participate in a 10-day simulated quadrotor UAV flight training exercise. The EEG power spectral density (PSD)-based metrics were used to investigate the changes in neural responses caused by variations in the mental workload at different stages of mental schema evolution.Main results. It was found that the mental schema evolution influenced the direction and change trends of the frontal theta PSD, parietal alpha PSD, and central beta PSD, which are EEG indicators of mental workload. Initially, before the mental schema was formed, only the frontal theta PSD increased with increasing task difficulty; when the mental schema was initially being developed, the frontal theta PSD and the parietal alpha PSD decreased with increasing task difficulty, while the central beta PSD increased with increasing task difficulty. Finally, as the mental schema gradually matured, the trend of the three indicators did not change with increasing task difficulty. However, differences in the frontal PSD became more pronounced across task difficulty levels, while differences in the parietal PSD narrowed.Significance. Our results describe the relationship between the EEG PSD and the mental workload of UAV operators as the mental schema evolved. This suggests that EEG activity can be used to identify the mental schema and mental workload experienced by operators while performing a task, which can not only provide more accurate measurements of mental workload but also provide insights into the development of an operator's skill level.

Multi-Omics Analysis of Transcriptomic and Metabolomics Profiles Reveal the Molecular Regulatory Network of Marbling in Early Castrated Holstein Steers.

The intramuscular fat (IMF), or so-called marbling, is known as potential determinant of the high quality beef in China, Korea, and Japan. Of the methods that affect IMF content in cattle, castration is markedly regarded as an effective and economical way to improve the deposition of IMF but with little attention to its multi-omics in early-castrated cattle. The aim of this study was to investigate the liver transcriptome and metabolome of early-castrated Holstein cattle and conduct a comprehensive analysis of two omics associated with the IMF deposition using transcriptomics and untargeted metabolomics under different treatments: non−castrated and slaughtered at 16 months of age (GL16), castrated at birth and slaughtered at 16 months of age (YL16), and castrated at birth and slaughtered at 26 months of age (YL26). The untargeted metabolome was analyzed using ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The transcriptome of the hepatic genes was analyzed to identify marbling-related genes. Using untargeted metabolomics, the main altered metabolic pathways in the liver of cattle, including those for lipid and amino acid metabolism, were detected in the YL16 group relative to the GL16 and YL26 groups. Significant increases in the presence of betaine, alanine, and glycerol 3-phosphate were observed in the YL16 group (p < 0.05), which might have contributed to the improved beef-marbling production. Compared to the GL16 and YL26 groups, significant increases in the presence of glutathione, acetylcarnitine, and riboflavin but decreases in diethanolamine and 2-hydroxyglutarate were identified in YL16 group (p < 0.05), which might have been beneficial to the beef's enhanced functional quality. The gene expressions of GLI1 and NUF2 were downregulated and that of CYP3A4 was upregulated in the YL16 group; these results were strongly correlated with the alanine, betaine, and leucine, respectively, in the liver of the cattle. In conclusion, implementation of early castration modified the hepatic metabolites and the related biological pathways by regulating the relevant gene expressions, which could represent a better rearing method for production of high marbled and healthier beef products.

Downregulation of HBx Restrains Proliferation, Migration, and Invasion of HepG2 Cells.

Liver cancer is a major contributor to cancer-related death with poor survival for sufferers. Meanwhile, Hepatic B virus X protein (HBx) and XB130 are likely to participate in the pathogenesis of liver cancer. However, the detailed mechanism of HBx/XB130 in liver cancer remains to be further investigated. Our study explored the effects of HBx/XB130 on liver cancer progression. HBx and XB130 expression was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot. Overexpression of HBx and XB130 was found in liver cancer tissues and cells. Mechanistic study revealed that HBx could bind to and positively regulate XB130 in HepG2 cells. Subsequently, HBx expression was knocked down, while XB130 was overexpressed in HepG2 cells in order to observe the specific role of HBx/XB130 in liver cancer in vitro. Results of CCK-8, Transwell, wound healing, and colony formation assays suggested that HBx could mediate biological function of HepG2 cells by activating the XB130-mediated PI3K/AKT pathway. In summary, our data illustrate that inhibition of HBx effectively suppressed proliferation and metastasis and induced apoptosis of liver cancer cells, which might be partially reversed by XB130. HBx and XB130 may be potential targets for liver cancer pathogenesis.