Measuring the dynamic balance of integration and segregation underlying consciousness, anesthesia, and sleep.

Consciousness requires a dynamic balance of integration and segregation in functional brain networks. An optimal integration-segregation balance depends on two key aspects of functional connectivity: global efficiency (i.e., integration) and clustering (i.e., segregation). We developed a new fMRI-based measure, termed the integration-segregation difference (ISD), which captures both aspects. We used this metric to quantify changes in brain state from conscious wakefulness to loss of responsiveness induced by the anesthetic propofol. The observed changes in ISD suggest a profound shift to segregation in both whole brain and all brain subnetworks during anesthesia. Moreover, brain networks displayed similar sequences of disintegration and subsequent reintegration during, respectively, loss and return of responsiveness. Random forest machine learning models, trained with the integration and segregation of brain networks, identified the awake vs. unresponsive states and their transitions with accuracy up to 93%. We found that metastability (i.e., the dynamic recurrence of non-equilibrium transient states) is more effectively explained by integration, while complexity (i.e., diversity and intricacy of neural activity) is more closely linked with segregation. The analysis of a sleep dataset revealed similar findings. Our results demonstrate that the integration-segregation balance is a useful index that can differentiate among various conscious and unconscious states.

Tumor-derived apoptotic extracellular vesicle-mediated intercellular communication promotes metastasis and stemness of lung adenocarcinoma.

Apoptosis has long been recognized as a significant mechanism for inhibiting tumor formation, and a plethora of stimuli can induce apoptosis during the progression and treatment of tumors. Moreover, tumor-derived apoptotic extracellular vesicles (apoEVs) are inevitably phagocytosed by live tumor cells, promoting tumor heterogeneity. Understanding the mechanism by which apoEVs regulate tumor cells is imperative for enhancing our knowledge of tumor metastasis and recurrence. Herein, we conducted a series of in vivo and in vitro experiments, and we report that tumor-derived apoEVs promoted lung adenocarcinoma (LUAD) metastasis, self-renewal and chemoresistance. Mechanistically, we demonstrated that apoEVs facilitated tumor metastasis and stemness by initiating the epithelial-mesenchymal transition program and upregulating the transcription of the stem cell factor SOX2. In addition, we found that ALDH1A1, which was transported by apoEVs, activated the NF-κB signaling pathway by increasing aldehyde dehydrogenase enzyme activity in recipient tumor cells. Furthermore, targeting apoEVs-ALDH1A1 significantly abrogated these effects. Collectively, our findings elucidate a novel mechanism of apoEV-dependent intercellular communication between apoptotic tumor cells and live tumor cells that promotes the formation of cancer stem cell-like populations, and these findings reveal that apoEVs-ALDH1A1 may be a potential therapeutic target and biomarker for LUAD metastasis and recurrence.

Propofol Disrupts the Functional Core-Matrix Architecture of the Thalamus in Humans.

Research into the role of thalamocortical circuits in anesthesia-induced unconsciousness is difficult due to anatomical and functional complexity. Prior neuroimaging studies have examined either the thalamus as a whole or focused on specific subregions, overlooking the distinct neuronal subtypes like core and matrix cells. We conducted a study of heathy volunteers and functional magnetic resonance imaging during conscious baseline, deep sedation, and recovery. We advanced the functional gradient mapping technique to delineate the functional geometry of thalamocortical circuits, within a framework of the unimodal-transmodal functional axis of the cortex. We observed a significant shift in this geometry during unconsciousness, marked by the dominance of unimodal over transmodal geometry. This alteration was closely linked to the spatial variations in the density of matrix cells within the thalamus. This research bridges cellular and systems-level understanding, highlighting the crucial role of thalamic core-matrix functional architecture in understanding the neural mechanisms of states of consciousness.

The neural correlates of arousal: Ventral posterolateral nucleus-global transient co-activation.

Arousal and awareness are two components of consciousness whose neural mechanisms remain unclear. Spontaneous peaks of global (brain-wide) blood-oxygenation-level-dependent (BOLD) signal have been found to be sensitive to changes in arousal. By contrasting BOLD signals at different arousal levels, we find decreased activation of the ventral posterolateral nucleus (VPL) during transient peaks in the global signal in low arousal and awareness states (non-rapid eye movement sleep and anesthesia) compared to wakefulness and in eyes-closed compared to eyes-open conditions in healthy awake individuals. Intriguingly, VPL-global co-activation remains high in patients with unresponsive wakefulness syndrome (UWS), who exhibit high arousal without awareness, while it reduces in rapid eye movement sleep, a state characterized by low arousal but high awareness. Furthermore, lower co-activation is found in individuals during N3 sleep compared to patients with UWS. These results demonstrate that co-activation of VPL and global activity is critical to arousal but not to awareness.

Psychedelic concentrations of nitrous oxide reduce functional differentiation in frontoparietal and somatomotor cortical networks.

Despite the longstanding use of nitrous oxide and descriptions of its psychological effects more than a century ago, there is a paucity of neurobiological investigation of associated psychedelic experiences. We measure the brain's functional geometry (through analysis of cortical gradients) and temporal dynamics (through analysis of co-activation patterns) using human resting-state functional magnetic resonance imaging data acquired before and during administration of 35% nitrous oxide. Both analyses demonstrate that nitrous oxide reduces functional differentiation in frontoparietal and somatomotor networks. Importantly, the subjective psychedelic experience induced by nitrous oxide is inversely correlated with the degree of functional differentiation. Thus, like classical psychedelics acting on serotonin receptors, nitrous oxide flattens the functional geometry of the cortex and disrupts temporal dynamics in association with psychoactive effects.

Social ecological model based analysis of sport exercise behaviors and associated factors among children and adolescents in Ningxia / 中国学校卫生

Objective@#To understand the influencing factors underlying physical exercise behavior among children and adolescents aged 9-18 years in Ningxia, China, in 2019, and to provide suggestions for physical exercise among children and adolescents by adopting a social ecological model.@*Methods@#Based on data related to 12 018 children and adolescents in Ningxia aged 9-18 years old which were obtained from the National Survey on Students Constitution and Health in 2019, the survey questions scored based on the four levels of the social ecological model.@*Results@#The proportion of children and adolescents who engaged in physical exercise for less than 1 hour a day accounted for 55.97% of the total number of people in Ningxia. Regardless of whether they were able to engage in enough physical activity, individual factors played a dominant role in influencing the behavior of the children and adolescents, and an interaction was found between influencing factors at different levels( r=-0.01, 0.01, -0.08, 0.04, P <0.01). The results of the stepwise regression analysis showed that the personal factors e.g. sports makes me healthy, I don t have enough time, muscle strength exercise, I have no movement of any relationship partner, sports make me know partner, policy in the number of physical education, number of sports meeting in a school year, the average daily lesson hold number all affect children s sports activities in time( B =-0.05-0.16, P <0.01).@*Conclusions@#The lack of physical exercise among children and adolescents in Ningxia is the result of multiple factors. Comprehensive and diversified intervention should be administered from a socio ecological framework to promote the formation of physical exercise habits among children and adolescents.

Correlation analysis between different nutritional status and age at first spermatorrhea of boys aged 11 to 18 in Ningxia in 2019 / 中国学校卫生

Objective@#To explore the correlation between obesity and first ejaculation in boys aged 11-18 years old in Ningxia in 2019, and to provide the theoretical reference for puberty development among obese boys.@*Methods@#Using the method of stratified random cluster sampling, 5 240 boys aged 11- 18 were selected from Yinchuan, Zhongwei, Wuzhong and Guyuan in Ningxia Hui Autonomous Region. Height, weight, and first ejaculation were obtained.Body mass index (BMI) was calculated to determine nutritional status, and the χ 2 test was used to compare the differences between groups of nutritional status; the probability unit regression method was used to calculater the soth percentile age at ejaculation, and the U test was applied to compare the differences in age at ejaculation between groups.@*Results@#The rates of overweight and obesity among boys aged 11 to 18 years in Ningxia Hui Autonomous Region in 2019 were 15.5% and 8.8%. The detection rate of overweight and obesity among urban boys was 17.8% and 10.5% and the detection rate of overweight and obesity among rural boys was 12.9% and 6.9%,respectively. The 50 th percentile age at half ejaculation among urban boys aged 11 to 18 years was 14.94 years; the 50 th percentile age at ejaculation among rural boys was 15.33 years( P <0.01). The 50 th percentile age at ejaculation was 15.61, 15.10, 15.05 and 15.05 years for boys in the wasted, normal weight, overweight and obese groups, respectively.@*Conclusion@#Nutritional status was not associated with age at first ejaculation in the present study,but warrants farther investigation.

Relationship between BMI nutritional status and physical fitness of children and adolescents aged 6-18 in Ningxia in 2019 / 中国学校卫生

Objective@#To understand the nutritional status and physical quality of children and adolescents aged 6-18 in Ningxia in 2019, so as to provide scientific basis for health promotion children and adolescents.@*Methods@#A total of 16 076 children and adolescents aged 6-18 years old from Ningxia were selected by multi stage stratified cluster random sampling. Weight, height and physical fitness indexes (50 m running, standing long jump, sitting forward flexion) were measured and analyzed. The Chi square test was carried out to compare differences between groups, and the relationship between nutritional status and physical fitness was assessed by Logistic regression models.@*Results@#In 2019, detection rate of stunting loss rate, overweight and obesity rate of children and adolescents aged 6-18 in Ningxia were 6.9%, 12.6% and 8.7%, respectively. The below average rates of sitting forward flexion, 50 m running and standing long jump were 10.0%, 8.6% and 26.7%, respectively, while the passing rates were 63.5%, 63.7% and 55.5%, respectively. The good rates were 14.7%, 11.7% and 12.3%, and the excellent rates were 11.8%, 16.0 % and 5.5%, respectively. The passing rates of sitting forward flexion, 50 m running and standing long jump in stunting group were lower than those in the normal weight group ( OR=0.75, 0.72, 0.77, P ＜0.05); the passing rates of 50 m run and standing long jump in the overweight group was lower than that of normal weight group ( OR=0.79, 0.52, P ＜0.05); the passing rates of sitting forward flexion, 50 m running and standing long jump in the obese group were lower than those in the normal weight group ( OR=0.73, 0.52, 0.32, P ＜0.05).@*Conclusion@#In 2019, children and adolescents in Ningxia have the doublel burden of stunting, overweight and obesity. Physical fitness is associated with nutritional status, suggesting weight control might be helpful to keep fitness among children and adolescents.

Trends of overweight and prevalence among Ningxia Han ethnic students during 2000-2019 / 中国学校卫生

Objective@#To investigate the trend of overweight and obesity among Han students aged 7-18 in Ningxia from the year of 2000 to 2019, and to provide scientific basis for obesity prevention and control among children and adolescents.@*Methods@#Based on the five waves of "National Student Physical Fitness and Health Survey" in Ningxia region during 2000 to 2019, body weight, height, waist circumference, hip circumference and other data of Han students aged 7-18 years were included was used for trend analysis.@*Results@#In 2019, the detection rates of overweight and obesity in children and adolescents aged 7 to 18 in Ningxia were 13.34% (1 181/8 855) and 9.19% (814/8 855), respectively. The increase rate of overweight and obesity in boys from 2000 to 2019 was 11.68% and 10.07% ( χ 2=27.60, P <0.01). The rate of overweight and obesity in female students from 2000 to 2019 was 6.95% and 5.77% ( χ 2=33.82, P <0.01). Urban boys had the highest rates of overweight and obesity, which were 11.38% and 10.45%. The growth rate of overweight and obesity in rural boys was higher than that in urban boys after 2010 ( χ 2=13.90,17.09, P < 0.05), and the growth rate of obesity in rural girls was higher than that in urban girls after 2014 ( χ 2=9.94, 33.39, P <0.05). Overweight and obesity prevalence showed positive associations with the economic status in both urban and rural areas ( χ 2=35.19, 35.35, P <0.01).@*Conclusion@#From 2000 to 2019, the prevalence of overweight and obesity and body mass index among children and adolescents in Ningxia increased consistently, with more rigirous in rural areas. Specific strategies and measures for overweight and obesity prevention in children and adolescents are in urgent need, to reduce potential social and economic burden.