Prognostic stratification of sepsis through DNA damage response based RiskScore system: insights from single-cell RNA-sequencing and transcriptomic profiling.

Background: A novel risk scoring system, predicated on DNA damage response (DDR), was developed to enhance prognostic predictions and potentially inform the creation of more effective therapeutic protocols for sepsis. Methods: To thoroughly delineate the expression profiles of DDR markers within the context of sepsis, an analytical approach utilizing single-cell RNA-sequencing (scRNA-seq) was implemented. Our study utilized single-cell analysis techniques alongside weighted gene co-expression network analysis (WGCNA) to pinpoint the genes that exhibit the most substantial associations with DNA damage response (DDR). Through Cox proportional hazards LASSO regression, we distinguished DDR-associated genes and established a risk model, enabling the stratification of patients into high- and low-risk groups. Subsequently, we carried out an analysis to determine our model's predictive accuracy regarding patient survival. Moreover, we examined the distinct biological characteristics, various signal transduction routes, and immune system responses in sepsis patients, considering different risk categories and outcomes related to survival. Lastly, we conducted experimental validation of the identified genes through in vivo and in vitro assays, employing RT-PCR, ELISA, and flow cytometry. Results: Both single-cell RNA sequencing (scRNA-seq) and bulk transcriptomic analyses have demonstrated a strong correlation between DNA damage response (DDR) levels and sepsis prognosis. Specific cell subtypes, including monocytes, megakaryocytes, CD4+ T cells, and neutrophils, have shown elevated DDR activity. Cells with increased DDR scores exhibited more robust and numerous interactions with other cell populations. The weighted gene co-expression network analysis (WGCNA) and single-cell analyses revealed 71 DDR-associated genes. We developed a four-gene risk scoring system using ARL4C, CD247, RPL7, and RPL31, identified through univariate COX, LASSO COX regression, and log-rank (Mantel-Cox) tests. Nomograms, calibration plots, and decision curve analyses (DCA) regarding these specific genes have provided significant clinical benefits for individuals diagnosed with sepsis. The study suggested that individuals categorized as lower-risk demonstrated enhanced infiltration of immune cells, upregulated expression of immune regulators, and a more prolific presence of immune-associated functionalities and pathways. RT-qPCR analyses on a sepsis rat model revealed differential gene expression predominantly in the four targeted genes. Furthermore, ARL4C knockdown in sepsis model in vivo and vitro caused increased inflammatory response and a worse prognosis. Conclusion: The delineated DDR expression landscape offers insights into sepsis pathogenesis, whilst our riskScore model, based on a robust four-gene signature, could underpin personalized sepsis treatment strategies.

Syntactic encoding in written language production by deaf writers: A structural priming study and a comparison with hearing writers.

In three structural priming experiments, we investigated whether deaf and hearing writers differ in the processes and representations underlying written language production. Experiment 1 showed that deaf writers of Mandarin Chinese exhibited comparable extents of structural priming and comparable lexical boosts, suggesting that syntactic encoding in written language production is similarly sensitive to prior lexical-syntactic experience in deaf and hearing writers. Experiment 2 showed that, while hearing writers showed a boost in structural priming when the prime and the target had homographic or heterographic homophone dative verbs compared to unrelated ones, deaf writers showed a homophone boost only with homographic homophone verbs but not with heterographic homophone verbs. This finding suggests that while hearing people develop associated lemmas for homophones due to phonological identity, deaf people do so due to orthographic identity. Finally, Experiment 3 showed no boost in structural priming in deaf writers or hearing writers when the prime and the target had the same verb of the same orthography (i.e., in the same script) than of different orthographies (i.e., between Simplified and Traditional Chinese), suggesting that neither hearing nor deaf people use orthographic identity to reactivate the prime structure. In all, the findings suggest that syntactic encoding in writing employs the same syntactic and lexical representations in deaf and hearing writers, though lexical representations are shaped more by orthography than phonology in deaf writers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Objective ages of acquisition for 3300+ simplified Chinese characters.

We report the construction of two age-of-acquisition (AoA) norms for 3300+ characters in simplified Chinese, which make up about 99% of the texts used in daily life. We determined a character's AoA according to the time in which the character is formally learned in two sets of leading textbooks of Chinese in compulsory education, published respectively on the basis of the 2001 and 2011 national curriculum. Apart from having a significantly larger coverage of characters than previous norms, the current norms also outperformed them in explaining accuracy and reaction times in four large-scale databases for character decision, character naming, or character handwriting, even after controlling for the effects of frequency, number of meanings, and number of strokes. The explanatory advantage of the current norms suggests that, compared to earlier norms, the current norms capture more up-to-date character AoAs; these findings also highlight the diachronic nature of some lexical variables such as AoA and frequency. The developed objective AoA norms can be used for subsequent research on Chinese character recognition or production.

Effect of Acute Moderate-Intensity Exercise on the Mirror Neuron System: Role of Cardiovascular Fitness Level.

OBJECTIVES: The aims of this study were to use functional near-infrared spectroscopy (fNIRS) to determine whether cardiovascular fitness levels modulate the activation of the mirror neuron system (MNS) under table-setting tasks in non-exercise situation, to replicate the study that positive effect of acute moderate-intensity exercise on the MNS and investigate whether cardiovascular fitness levels modulates the effect of exercise on the activation of the MNS. METHODS: Thirty-six healthy college-aged participants completed a maximal graded exercise test (GXT) and were categorized as high, moderate, or low cardiovascular fitness. Participants then performed table-setting tasks including an action execution task (EXEC) and action observation task (OBS) prior to (PRE) and after (POST) either a rest condition (CTRL) or a cycling exercise condition (EXP). The EXP condition consisted of a 5-min warm-up, 15-min moderate-intensity exercise (65% VO2 max), and 5-min cool-down. RESULTS: No significant differences were observed for Oxy-Hb and Deoxy-Hb between different cardiovascular fitness levels in the EXEC or OBS tasks in the non-exercise session. But there were significant improvements of oxygenated hemoglobin (Oxy-Hb) in the inferior frontal gyrus (IFG) and pre-motor area (PMC) regions under the OBS task following the acute moderate exercise. Particularly, the improvements (Post-Pre) of Δ Oxy-Hb were mainly observed in high and low fitness individuals. There was also a significant improvement of deoxygenated hemoglobin (Deoxy-Hb) in the IPL region under the OBS task. The following analysis indicated that exercise improved Δ Deoxy-Hb in high fitness individuals. CONCLUSION: This study indicated that the activation of MNS was not modulated by the cardiovascular fitness levels in the non-exercise situation. We replicated the previous study that moderate exercise improved activation of MNS; we also provided the first empirical evidence that moderate-intensity exercise positively affects the MNS activation in college students of high and low cardiovascular fitness levels.

Effect of a Combined Exercise and Dietary Intervention on Self-Control in Obese Adolescents.

OBJECTIVE: The aim of this study was to determine whether a combined exercise and dietary intervention improved cognitive and physical self-control and whether pre-to-post interventional changes in self-control were mediated by changes in body mass index (BMI) and maximal grip strength (MGS), in a sample of obese adolescents. METHODS: Forty-four obese adolescents were randomly assigned to a combined exercise and dietary program or to a waitlist control group; the data from 36 participants (n = 18 for each group) were analyzed. The combined exercise and dietary program was performed over 6 weeks and was supervised by qualified trainers in a closed boot camp. The exercise consisted primarily of typical aerobic training, sports, outdoor training, yoga, and resistance training. Participants were placed on moderate dietary restriction according to individual target body weight (30 kcal/kg × target weight). The primary outcomes of this study were metrics based on cognitive and physical self-control, assessed by the Stroop task and a handgrip task, respectively. Secondary outcomes included BMI and MGS. RESULTS: The combined exercise and dietary intervention significantly improved both cognitive and physical self-control. Similar positive effects were also found for reduced BMI and enhanced MGS. Correlation analyses showed that the reduced BMI and enhanced MGS were significantly closely associated with improved cognitive and physical self-control. The mediation analyses revealed that the pre-to-post intervention changes in BMI and MGS significantly mediated physical self-control, but did not mediate cognitive self-control. CONCLUSION: Our combined exercise and dietary intervention is an effective approach to improve multiple aspects of self-control, reduce BMI, and strengthen MGS among obese adolescents. These findings also suggest that reduced BMI and enhanced MGS mediate specific aspects of self-control.

The Positive Effect of Moderate-Intensity Exercise on the Mirror Neuron System: An fNIRS Study.

A growing number of studies have reported the beneficial effect of exercise on human social behavior. The mirror neuron system (MNS) plays a critical role in a variety of social behaviors from imitation to empathy. However, neuroimaging investigations into the effects of exercise on the MNS remain unexplored. To address this question, our study determined the effect of moderate-intensity exercise on the MNS using functional near-infrared spectroscopy (fNIRS). Specifically, 23 right-handed young individuals were asked to perform a table-setting task that included action execution and action observation before and after a 25-min exercise session on a cycle ergometer at moderate intensity (65% VO2peak). The control condition was the same task performed without exercise. Cortical hemodynamic changes in the four primary brain regions of the MNS were monitored with fNIRS, using a modified probe configuration that covered all four MNS regions in the left hemisphere. We used a region of interest (ROI)-based group analysis to determine which regions were activated during action execution and action observation. Following a session of moderate-intensity exercise, we found a significant increase in activation in all four MNS regions, namely the inferior frontal gyrus (IFG), premotor cortex (PMC), superior parietal lobule (SPL), and rostral inferior parietal lobule (IPL). This result indicated a positive effect of exercise on the MNS, specifically that moderate-intensity exercise could activate the MNS.

Sedentary Behavior and Problematic Smartphone Use in Chinese Adolescents: The Moderating Role of Self-Control.

This study investigated smartphone use characteristics including the purpose of smartphone use (i.e., leisure, learning, or work) and situational smartphone use (i.e., sitting, standing, or moving about) in Chinese adolescents. Moreover, it tested the moderating role of self-control in the link between sedentary behavior and problematic smartphone use. A total of 947 adolescents completed measures of the purpose of their smartphone use, situational smartphone use, sedentary behavior, self-control, time on smartphone, and smartphone addiction. Results showed that the majority of smartphone use was for leisure and learning, and 90.9% of adolescents reported typically sitting as they used the smartphone. Problematic smartphone use was positively correlated with sedentary behavior and negatively correlated with self-control. Moreover, the relationship between sedentary behavior and problematic smartphone use was moderated by self-control, in that the negative correlation was stronger for adolescents with low self-control and weaker for those with high self-control. These results contribute to the understanding of when sedentary behavior is associated with problematic smartphone use. Several limitations and implications are discussed in this study.