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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. Like classical psychedelics, nitrous oxide reduces functional differentiation in human frontoparietal and somatomotor networks, flattening functional brain geometry and disrupting temporal dynamics in association with the psychedelic experience. [ABSTRACT FROM AUTHOR]

In this paper, we take the Yangtze River Economic Belt as the study area and analyze three types of environmental regulation tools, namely, command-and-control (CAC), market-incentivized (MI) and public-type (PT). We apply the threshold effect to test the impact of each of these tools on regional economic growth and analyze the relationships between the tools and environmental regulation. The entropy method is used to calculate the comprehensive environmental pollution index of each province and city in the Yangtze River Economic Belt. Using Stata 14.0 measurement software and based on provincial data with respect to the Yangtze River Economic Belt from 2014 to 2021, a panel threshold model is used to test the impact of the three types of environmental regulation tools on regional economic growth and analyze the relationship between environmental regulation and regional economic growth. It is found that the relationship between environmental regulation and economic growth is non-linear. There is no significant relationship between CAC environmental regulation and regional economic growth; there is a single threshold effect between market-incentive environmental regulation and public participation environmental regulation on the economic growth of the Yangtze River economic belt. [ABSTRACT FROM AUTHOR]

In the present research, the accelerated test using the stepped isothermal method (SIM) was applied to characterize the long‐term compressive behavior of laminated bamboo. Generating a creep master curve using the SIM data is somewhat empirical. In particular, the selection of the end and beginning segments in the rescaling process is not standardized, which will affect the determination of virtual time. The variability of the virtual time influences the construction of master curves, thus leading to errors in predicting long‐term behavior. The difference in selecting the end and beginning segments was studied in terms of the virtual time, rescaled isothermal curves, and master curves. A 40% end segment and a 30% beginning segment were recommended to build a more accurate master curve. The generated master curves showed repeatability and matched reasonably well with the conventional creep results. It indicates that SIM is a reliable tool for the accelerated test of the long‐term behavior of laminated bamboo. In addition, isochronous stress‐creep strain curves were constructed based on the master curves at different loadings to provide evidence to determine stress levels for structural design. [ABSTRACT FROM AUTHOR]

Time and space are fundamental elements that permeate the fabric of nature, and their significance in relation to neural activity and consciousness remains a compelling yet unexplored area of research. The Temporospatial Theory of Consciousness (TTC) provides a framework that links time, space, neural activity, and consciousness, shedding light on the intricate relationships among these dimensions. In this review, I revisit the fundamental concepts and mechanisms proposed by the TTC, with a particular focus on the central concept of temporospatial nestedness. I propose an extension of temporospatial nestedness by incorporating the nested relationship between the temporal circuit and functional geometry of the brain. To further unravel the complexities of temporospatial nestedness, future research directions should emphasize the characterization of functional geometry and the temporal circuit across multiple spatial and temporal scales. Investigating the links between these scales will yield a more comprehensive understanding of how spatial organization and temporal dynamics contribute to conscious states. This integrative approach holds the potential to uncover novel insights into the neural basis of consciousness and reshape our understanding of the world–brain dynamic. [ABSTRACT FROM AUTHOR]

Polymers with relatively higher thermal conductivity are in great demand for many advanced functional applications that often require thermally conductive as well as flexible materials. However, enhancing the thermal conductivity of polymers, while maintaining their mechanical properties, is still a formidable challenge. Here it is reported on the successful fabrication of polyethylene (PE)/boron nitride nanoplate (BNNP) nanocomposite films, with excellent flexibility and ultrahigh through‐plane thermal conductivity, by a uniaxially hot‐stretching process. Results from this study show that the nanocomposite films with ϕv = 6.7 vol% BNNPs, under low stretching ratio (Λ = 5), exhibit a through‐plane thermal conductivity of ≈14.54 W m−1 K−1, about 44.4 times higher than the corresponding bulk value for PE (0.32 W m−1 K−1), while also having improved the Young's modulus of elasticity. The theoretical analysis also shows that such a dramatic enhancement can be attributed to the formation of a 3D continuous network structure within the nanocomposite films. Thus, these flexible films offer possibilities as passive heat exchange matrices in various advanced applications that often require the materials with higher flexibility, lighter weight, easy/scalable processing attributes, and with a higher thermal conductivity. [ABSTRACT FROM AUTHOR]

Pulmonary stenosis (PS) is a congenital heart disease characterized by a dynamic or fixed anatomic obstruction of blood flow from the right ventricle to the pulmonary arterial vasculature. In the present study, extracellular vesicle long RNAs (EVLRs) from pregnant females who had healthy infants or PS infants were analyzed by RNA sequencing, and their diagnostic potential for PS during pregnancy was evaluated. A method for the selection of genes that could be considered as informative for the prediction PS based on extracellular vesicles (EVs) from pregnant females using long-read RNA sequencing was developed. Blood samples were collected from females carrying fetuses with PS and females carrying unaffected fetuses (n=6 in each group). Physical characterization of EVs was performed using nanoparticle tracking analysis, transmission electron microscopy and western blotting. EVLRs from plasma were profiled by RNA sequencing and mRNA co-expression modules were constructed by weighted gene co-expression network analysis (WGCNA). Gene Ontology (GO) enrichment analysis was used to predict the function of the genes in each module. Hub genes were filtered out based on WGCNA and visualized using Cytoscape. EVLRs consisted of mRNAs, microRNAs and long non-coding RNA. Overall, 26 modules were identified containing 16,394 genes. All modules were independent of each other. One particular module, referred to as the blue module, was markedly different between the two groups. A total of 735 hub genes in the blue module were identified, of which 33 were visualized, demonstrating the connection between these hub genes. GO enrichment analysis demonstrated that the analyzed hub genes were enriched in 'glucose transport', 'ATP-dependent chromatin remodeling', 'histone deacetylation', 'histone H3-K4 methylation', 'DNA methylation', 'apoptotic signaling pathway' and 'glucocorticoid receptor signaling pathway'. The hub genes identified in this module may provide a genetic framework for prenatal PS diagnosis. Furthermore, functional analysis of these associated genes may provide a theoretical basis for further research on PS pathogenesis. [ABSTRACT FROM AUTHOR]

Recent resting-state functional MRI (fMRI) studies have revealed that the global signal (GS) exhibits a nonuniform spatial distribution across the gray matter. Whether this topography is informative remains largely unknown. We therefore tested rest-task modulation of GS topography by analyzing static GS correlation and dynamic coactivation patterns in a large sample of an fMRI dataset (n = 837) from the Human Connectome Project. The GS topography in the resting state and in seven different tasks was first measured by correlating the GS with the local time series (GSCORR). In the resting state, high GSCORR was observed mainly in the primary sensory and motor regions, whereas low GSCORR was seen in the association brain areas. This pattern changed during the seven tasks, with mainly decreased GSCORR in sensorimotor cortex. Importantly, this rest-task modulation of GSCORR could be traced to transient coactivation patterns at the peak period of GS (GS-peak). By comparing the topography of GSCORR and respiration effects, we observed that the topography of respiration mimicked the topography of GS in the resting state, whereas both differed during the task states; because of such partial dissociation, we assume that GSCORR could not be equated with a respiration effect. Finally, rest-task modulation of GS topography could not be exclusively explained by other sources of physiological noise. Together, we here demonstrate the informative nature of GS topography by showing its rest-task modulation, the underlying dynamic coactivation patterns, and its partial dissociation from respiration effects during task states. Recent resting-state fMRI studies have shown that the global signal exhibits a nonuniform spatial distribution across gray matter, but is this informative? This neuroimaging study reveals novel insights into the informative nature of global signal by rest-task modulation of the global signal topography. [ABSTRACT FROM AUTHOR]

Background: Consciousness is supported by integrated brain activity across widespread functionally segregated networks. The functional magnetic resonance imaging-derived global brain signal is a candidate marker for a conscious state, and thus the authors hypothesized that unconsciousness would be accompanied by a loss of global temporal coordination, with specific patterns of decoupling between local regions and global activity differentiating among various unconscious states.Methods: Functional magnetic resonance imaging global signals were studied in physiologic, pharmacologic, and pathologic states of unconsciousness in human natural sleep (n = 9), propofol anesthesia (humans, n = 14; male rats, n = 12), and neuropathological patients (n = 21). The global signal amplitude as well as the correlation between global signal and signals of local voxels were quantified. The former reflects the net strength of global temporal coordination, and the latter yields global signal topography.Results: A profound reduction of global signal amplitude was seen consistently across the various unconscious states: wakefulness (median [1st, 3rd quartile], 0.46 [0.21, 0.50]) versus non-rapid eye movement stage 3 of sleep (0.30 [0.24, 0.32]; P = 0.035), wakefulness (0.36 [0.31, 0.42]) versus general anesthesia (0.25 [0.21, 0.28]; P = 0.001), healthy controls (0.30 [0.27, 0.37]) versus unresponsive wakefulness syndrome (0.22 [0.15, 0.24]; P < 0.001), and low dose (0.07 [0.06, 0.08]) versus high dose of propofol (0.04 [0.03, 0.05]; P = 0.028) in rats. Furthermore, non-rapid eye movement stage 3 of sleep was characterized by a decoupling of sensory and attention networks from the global network. General anesthesia and unresponsive wakefulness syndrome were characterized by a dissociation of the majority of functional networks from the global network. This decoupling, however, was dominated by distinct neuroanatomic foci (e.g., precuneus and anterior cingulate cortices).Conclusions: The global temporal coordination of various modules across the brain may distinguish the coarse-grained state of consciousness versus unconsciousness, while the relationship between the global and local signals may define the particular qualities of a particular unconscious state. [ABSTRACT FROM AUTHOR]

• A model for analyzing rolling shear stress for out-of-plane bending CLT panels was developed. • Formula for calculating shear capacity of CLT bending member was derived. • The proposed model is easier for calculating than current model but retain its accuracy. When used as horizontal components to carry vertical loads, such as floors and beams, the design of cross-laminated timber (CLT) panels is driven by out-of-plane bending. In this case, rolling shear is always one of the major concerns that governs the performances of ultimate limit state of CLT members. Analytical models are available for predicting the shear capacity of CLT panels, but they are computational extensive and cannot provide the longitudinal distribution of shear stress which is necessary to predict where the failure will happen. In this paper, a layered beam-based analytical model, for analyzing the stress of rolling shear for transversely loaded CLT members was developed. The model deems that the shear deformations of out-of-plane bending CLT members are carried by cross layers while the deformations of bending moment are carried by parallel layers. Based on the layered beam theory, the equation that governs the stress of rolling shear and its analytical solution were derived. It was found that the shear stress distribution in CLT longitudinal direction obeys exponential law and the maximum shear stress is located at the end of the CLT member. Formulas to predict the shear capacity for 3- and 5-layer CLT panels under out-of-plane bending were obtained. The proposed method was validated by the experimental data generated by the authors and by other researchers. Comparing to the shear analogy method and Gamma method, the proposed method requires less computational work and provides similar accuracy. [ABSTRACT FROM AUTHOR]

• An analytical model for ENF mode II fracture analysis was developed. • Bi-linear cohesive parameters of the composite can be determined through the model. • The model allows to determine G IIc with no need of data reduction. • R-curve can be analytically obtained. The complicated toughening mechanism of Mode II cracking in end notch flexure (ENF) test for fibrous composites prevents the existence of clear crack-tip. Hence the concept of equivalent linear crack length was proposed to avoid detecting the crack-tip in ENF test, which assumes that the increase of compliance due to the development of fracture process zone (FPZ) or crack propagation is attributed to the equivalent elastic crack length giving the same compliance as the one of the actual crack with its FPZ; thus the equivalent crack length can be estimated according to the associated compliance obtained from experiment. The objective of the presented work was to develop an analytical model for the analysis of ENF test specimen without need for crack-tip identification and complicated data reduction. Bilinear cohesive law was employed to model the cohesive force across the potential crack interfaces. Analytical solutions for the governing equation were derived. Furthermore, methods to determine the cohesive parameters, the length of fracture process zone (FPZ), and the energy release rate were developed. The critical loads corresponding to the damage and crack onset can also be estimated by the model. Experimental validation was implemented and a good agreement was achieved between the test results and model predictions. It can be concluded that bilinear cohesive law may achieve a good approximation for the tangential traction-separation constitutive relationship in Mode II fracture; the shear strength of the material can be taken as the critical stress of cracking onset; the energy release rate depends on the initial crack length to some extent, and this effect could be reduced as the length of initial crack increases. [ABSTRACT FROM AUTHOR]

Variability quenching is a widespread neural phenomenon in which trial‐to‐trial variability (TTV) of neural activity is reduced by repeated presentations of a sensory stimulus. However, its neural mechanism and functional significance remain poorly understood. Recurrent network dynamics are suggested as a candidate mechanism of TTV, and they play a key role in consciousness. We thus asked whether the variability‐quenching phenomenon is related to the level of consciousness. We hypothesized that TTV reduction would be compromised during reduced level of consciousness by propofol anesthetics. We recorded functional magnetic resonance imaging signals of resting‐state and stimulus‐induced activities in three conditions: wakefulness, sedation, and unconsciousness (i.e., deep anesthesia). We measured the average (trial‐to‐trial mean, TTM) and variability (TTV) of auditory stimulus‐induced activity under the three conditions. We also examined another form of neural variability (temporal variability, TV), which quantifies the overall dynamic range of ongoing neural activity across time, during both the resting‐state and the task. We found that (a) TTM deceased gradually from wakefulness through sedation to anesthesia, (b) stimulus‐induced TTV reduction normally seen during wakefulness was abolished during both sedation and anesthesia, and (c) TV increased in the task state as compared to resting‐state during both wakefulness and sedation, but not anesthesia. Together, our results reveal distinct effects of propofol on the two forms of neural variability (TTV and TV). They imply that the anesthetic disrupts recurrent network dynamics, thus prevents the stabilization of cortical activity states. These findings shed new light on the temporal dynamics of neuronal variability and its alteration during anesthetic‐induced unconsciousness. [ABSTRACT FROM AUTHOR]

Abstract: Which temporal features that can characterize different brain states (i.e., consciousness or unconsciousness) is a fundamental question in the neuroscience of consciousness. Using resting‐state functional magnetic resonance imaging (rs‐fMRI), we investigated the spatial patterns of two temporal features: the long‐range temporal correlations (LRTCs), measured by power‐law exponent (PLE), and temporal variability, measured by standard deviation (SD) during wakefulness and anesthetic‐induced unconsciousness. We found that both PLE and SD showed global reductions across the whole brain during anesthetic state comparing to wakefulness. Importantly, the relationship between PLE and SD was altered in anesthetic state, in terms of a spatial “decoupling.” This decoupling was mainly driven by a spatial pattern alteration of the PLE, rather than the SD, in the anesthetic state. Our results suggest differential physiological grounds of PLE and SD and highlight the functional importance of the topographical organization of LRTCs in maintaining an optimal spatiotemporal configuration of the neural dynamics during normal level of consciousness. The central role of the spatial distribution of LRTCs, reflecting temporo‐spatial nestedness, may support the recently introduced temporo‐spatial theory of consciousness (TTC). [ABSTRACT FROM AUTHOR]

The scale-free dynamics of human brain activity, characterized by an elaborate temporal structure with scale-free properties, can be quantified using the power-law exponent (PLE) as an index. Power laws are well documented in nature in general, particularly in the brain. Some previous fMRI studies have demonstrated a lower PLE during cognitive-task-evoked activity than during resting state activity. However, PLE modulation during cognitive-task-evoked activity and its relationship with an associated behavior remain unclear. In this functional fMRI study in the resting state and face processing + control task, we investigated PLE during both the resting state and task-evoked activities, as well as its relationship with behavior measured using mean reaction time (mRT) during the task. We found that (1) face discrimination-induced BOLD signal changes in the medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), amygdala, and fusiform face area; (2) PLE significantly decreased during task-evoked activity specifically in mPFC compared with resting state activity; (3) most importantly, in mPFC, mRT significantly negatively correlated with both resting state PLE and the resting-task PLE difference. These results may lead to a better understanding of the associations between task performance parameters (e.g., mRT) and the scale-free dynamics of spontaneous and task-evoked brain activities. [ABSTRACT FROM AUTHOR]

Aims This study aimed to investigate potential candidates and molecular mechanisms of myocardial ischemia/reperfusion (I/R) injury (MIRI) in type 2 diabetes mellitus. Main methods Type 2 diabetic and myocardial I/R mouse models were established with a high fat-diet (HFD) for 24 weeks and subjecting to global ischemia/reperfusion for 1 h/3 h, respectively. Microarray analysis was applied to screen differentially expressed genes (DEGs) in the hearts of these mice. Moreover, H9c2 cells were treated with high glucose (HG) and/or hypoxia and reoxygenation (H/R). Subsequently, the expression of suppressor of cytokine signaling 2 (SOCS2) was knocked down by siRNA followed by the above treatments. Then, the cell lipid peroxidation and apoptosis-related indicators (malondialdehyde, MDA, and lactate dehydrogenase, LDH, cleaved-caspase-3; glucose-regulated protein 78, GRP78;), Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling pathway-related proteins (p-JAK2 and p-STAT5b) and insulin-like growth factor-1 (IGF-1) were detected. Key findings The mRNA levels of selected DEGs, such as Angptl4 , Gadd45b , Rnf122 and SOCS2 , showed a high degree of correlation with the microarray data. In addition, the levels of SOCS2, caspase-3, GRP78, LDH and MDA were increased, while the IGF-1 level was down-regulated in cells treated with HG and/or H/R compared to untreated cells ( p < 0.05). However, SOCS2 knockdown elevated the expression levels of IGF-1, p-JAK2 and p-STAT5b, as well as caspase-3, GRP78, LDH and MDA. Significance This research suggests that overexpressed SOCS2 might exacerbates MIRI in type 2 diabetes mellitus by inhibiting the expression of IGF-1 via the JAK-STAT signaling pathway. [ABSTRACT FROM AUTHOR]

Time and space are the basic building blocks of nature. As a unique existent in nature, our brain exists in time and takes up space. The brain’s activity itself also constitutes and spreads in its own (intrinsic) time and space that is crucial for consciousness. Consciousness is a complex phenomenon including different dimensions: level/state, content/form, phenomenal aspects, and cognitive features. We propose a Temporo-spatial Theory of Consciousness (TTC) focusing primarily on the temporal and spatial features of the brain activity. We postulate four different neuronal mechanisms accounting for the different dimensions of consciousness: (i) “temporo-spatial nestedness” of the spontaneous activity accounts for the level/state of consciousness as neural predisposition of consciousness (NPC); (ii) “temporo-spatial alignment” of the pre-stimulus activity accounts for the content/form of consciousness as neural prerequisite of consciousness (preNCC); (iii) “temporo-spatial expansion” of early stimulus-induced activity accounts for phenomenal consciousness as neural correlates of consciousness (NCC); (iv) “temporo-spatial globalization” of late stimulus-induced activity accounts for the cognitive features of consciousness as neural consequence of consciousness (NCCcon). [ABSTRACT FROM AUTHOR]

Brain plasticity studies have shown functional reorganization in participants with outstanding motor expertise. Little is known about neural plasticity associated with exceptionally long motor training or of its predictive value for motor performance excellence. The present study utilised resting-state functional magnetic resonance imaging (rs-fMRI) in a unique sample of world-class athletes: Olympic, elite, and internationally ranked swimmers (n=30). Their world ranking ranged from 1st to 250th: each had prepared for participation in the Olympic Games. Combining rs-fMRI graph-theoretical and seed-based functional connectivity analyses, it was discovered that the thalamus has its strongest connections with the sensorimotor network in elite swimmers with the highest world rankings (career best rank: 1–35). Strikingly, thalamo-sensorimotor functional connections were highly correlated with the swimmers’ motor performance excellence, that is, accounting for 41% of the individual variance in best world ranking. Our findings shed light on neural correlates of long-term athletic performance involving thalamo-sensorimotor functional circuits. [ABSTRACT FROM AUTHOR]

• Combined out-of-plane bending and compression is an inevitable loading condition for CLT walls. • The experimental program consisted of 36 CLT panel specimens. • The damage was caused by the local buckling near the mid-height of the outer layer on the compression side. • Signs of shear failure of cross layers were evident almost simultaneously with the outer layer failure. • The interaction equations specified in the Canadian design standard are appropriate for the CLT panels under small load eccentricities. Combined out-of-plane bending and compression is an inevitable loading condition for cross-laminated timber (CLT) walls due to the out of plumbness, initial panel curvature and load eccentricity. Because of the weaker cross layers, the mechanical performance and failure mode of the CLT panels under such loading significantly differ from those of the other wood members, such as sawn timber and glulam. This experimental study focuses on investigating the behavior of CLT panels under the stated loading scenario. The experimental program consisted of 36 specimens, including 12 five-layer CLT panels provided by two Canadian manufacturers, as well as 12 three-layer and 12 five-layer CLT panels provided by a Chinese manufacturer. All the specimens were tested in Canada and China, respectively, using the same test setup. It was found that in the majority of the specimens, the damage was caused by the local buckling near the mid-height of the outer layer on the concave compression side at about 45%–60% of the ultimate failure load and 25%–35% of the ultimate deflection. The dominant failure mode was characterized as the crushing yield of the outer layer on the concave side (fibers in compression) near the mid-height after the local buckling progressed. Signs of shear failure of cross layers were evident almost simultaneously with the outer layer failure. Hence, although the dominant failure mode was likely triggered by the fracture in the cross layers due to rolling shear, the load-carrying capacity of the CLT panels under the combined out-of-plane bending and compression is governed by the compression failure of the longitudinal outer layers. It was found that a cross-layered panel can maintain its integrity before failure. It was also noted that the interaction equations specified in the Canadian design standard are appropriate for the CLT panels under small load eccentricity, while for panels that have large load eccentricity, the appropriateness of the interaction equation is questionable. Based on the test results obtained, the validity of the interaction equation for the prediction of the load-carrying capacity of CLT columns, specified in the CSA O86-19, is confirmed for cases in which P f / P r > 0.5 and M f / M r < 0.3. For the cases of P f / P r < 0.5 and M f / M r > 0.3 , modification of the equation is needed. [ABSTRACT FROM AUTHOR]

A new type of hollow deck made of laminated bamboo (LB) composite is reported in this study. Mechanical properties of LB composite in longitudinal direction and the bending performances of LB hollow desks were studied by experiments. It was found that for LB composite, the tensile strength is much higher than compressive strength; the tensile constitutive law exhibits perfectly elastic behavior whereas the compressive constitutive law exhibits liner behavior initially while turning to nonlinear manner once the stress exceeds the linear limit. The nonlinearity of compressive constitutive law may be modeled by parabolic curve. The accumulation of plastically compressive damage of LB composite in compressive zone leads to pronounced nonlinearity in bending LB decks. Failure of LB decks was dominated by tensile breakage in the outmost of convex side at critical section. Based on the nonlinearity and failure mechanisms, an inelastic model for LB deck analysis was developed in this study. The model can be used to evaluate the load-carrying capacities and deformations in service ability as well as in ultimate state. Good agreements were achieved between the results of model prediction and experiments. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated an overlap between the neural substrate of resting-state activity and self-related processing in the cortical midline structures (CMS). However, the neural and psychological mechanisms mediating this so-called “rest-self overlap” remain unclear. To investigate the neural mechanisms, we estimated the temporal structure of spontaneous/resting-state activity, e.g. its long-range temporal correlations or self-affinity across time as indexed by the power-law exponent (PLE). The PLE was obtained in resting-state activity in the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) in 47 healthy subjects by functional magnetic resonance imaging (fMRI). We performed correlation analyses of the PLE and Revised Self-Consciousness Scale (SCSR) scores, which enabled us to access different dimensions of self-consciousness and specified rest-self overlap in a psychological regard. The PLE in the MPFC's resting-state activity correlated with private self-consciousness scores from the SCSR. Conversely, we found no correlation between the PLE and the other subscales of the SCSR (public, social) or between other resting-state measures, including functional connectivity, and the SCSR subscales. This is the first evidence for the association between the scale-free dynamics of resting-state activity in the CMS and the private dimension of self-consciousness. This finding implies the relationship of especially the private dimension of self with the temporal structure of resting-state activity. [ABSTRACT FROM AUTHOR]

Two aspects of the low frequency fluctuations of spontaneous brain activity have been proposed which reflect the complex and dynamic features of resting-state activity, namely temporal variability and signal synchronization. The relationship between them, especially its role in consciousness, nevertheless remains unclear. Our study examined the temporal variability and signal synchronization of spontaneous brain activity, as well as their relationship during loss of consciousness. We applied an intra-subject design of resting-state functional magnetic resonance imaging (rs-fMRI) in two conditions: during wakefulness, and under anesthesia with clinical unconsciousness. In addition, an independent group of patients with disorders of consciousness (DOC) was included in order to test the reliability of our findings. We observed a global reduction in the temporal variability, local and distant brain signal synchronization for subjects during anesthesia. Importantly, we found a link between temporal variability and both local and distant signal synchronizations during wakefulness: the higher the degree of temporal variability, the higher its intra-regional homogeneity and inter-regional functional connectivity. In contrast, this link was broken down under anesthesia, implying a decoupling between temporal variability and signal synchronization; this decoupling was reproduced in patients with DOC. Our results suggest that there exist some as yet unclear physiological mechanisms of consciousness which “couple” the two mathematically independent measures, temporal variability and signal synchronization of spontaneous brain activity. Our findings not only extend our current knowledge of the neural correlates of anesthetic-induced unconsciousness, but have implications for both computational neural modeling and clinical practice, such as in the diagnosis of loss of consciousness in patients with DOC. [ABSTRACT FROM AUTHOR]

Recent functional magnetic resonance spectroscopy (fMRS) studies have shown changes in glutamate/glutamine (Glx) concentrations between resting-state and active-task conditions. However, the types of task used have been limited to sensory paradigms, and the regions from which Glx concentrations have been measured limited to sensory ones. This leaves open the question as to whether the same effect can be seen in higher-order brain regions during cognitive tasks. Cortical midline structures, especially the medial prefrontal cortex (MPFC), have been suggested to be involved in various such cognitive tasks. We, therefore set out to use fMRS to investigate the dynamics of Glx concentrations in the MPFC between resting-state and mental imagery task conditions. The auditory cortex was used as a control region. In addition, functional magnetic resonance imaging was used to explore task-related neural activity changes. The mental imagery task consisted of imagining swimming and was applied to a large sample of healthy participants ( n = 46). The participants were all competitive swimmers, ensuring proficiency in mental-swimming. Glx concentrations in the MPFC increased during the imagery task, as compared to resting-state periods preceding and following the task. These increases mirror BOLD activity changes in the same region during the task. No changes in either Glx concentrations or BOLD activity were seen in the auditory cortex. These findings contribute to our understanding of the biochemical basis of generating or manipulating mental representations and the MPFC's role in this. Hum Brain Mapp 36:3204-3212, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

• FFA engages in tactile face processing even after a decade of early-onset blindness. • Early visual experience primes cross-modal face specialization in the FFA. • Absence or extensive visual experience declines cross-modal face specialization. The fusiform face area (FFA) is a core cortical region for face information processing. Evidence suggests that its sensitivity to faces is largely innate and tuned by visual experience. However, how experience in different time windows shape the plasticity of the FFA remains unclear. In this study, we investigated the role of visual experience at different time points of an individual's early development in the cross-modal face specialization of the FFA. Participants (n = 74) were classified into five groups: congenital blind, early blind, late blind, low vision, and sighted control. Functional magnetic resonance imaging data were acquired when the participants haptically processed carved faces and other objects. Our results showed a robust and highly consistent face-selective activation in the FFA region in the early blind participants, invariant to size and level of abstraction of the face stimuli. The cross-modal face activation in the FFA was much less consistent in other groups. These results suggest that early visual experience primes cross-modal specialization of the FFA, and even after the absence of visual experience for more than 14 years in early blind participants, their FFA can engage in cross-modal processing of face information. [ABSTRACT FROM AUTHOR]

Recent studies at the cellular and regional levels have pointed out the multifaceted importance of neural synchronization and temporal variance of neural activity. For example, neural synchronization and temporal variance has been shown by us to be altered in patients in the vegetative state (VS). This finding nonetheless leaves open the question of whether these abnormalities are specific to VS or rather more generally related to the absence of consciousness. The aim of our study was to investigate the changes of inter- and intra-regional neural synchronization and temporal variance of resting state activity in anesthetic-induced unconsciousness state. Applying an intra-subject design, we compared resting state activity in functional magnetic resonance imaging (fMRI) between awake versus anesthetized states in the same subjects. Replicating previous studies, we observed reduced functional connectivity within the default mode network (DMN) and thalamocortical network in the anesthetized state. Importantly, intra-regional synchronization as measured by regional homogeneity (ReHo) and temporal variance as measured by standard deviation (SD) of the BOLD signal were significantly reduced in especially the cortical midline regions, while increased in the lateral cortical areas in the anesthetized state. We further found significant frequency-dependent effects of SD in the thalamus, which showed abnormally high SD in Slow-5 (0.01-0.027 Hz) in the anesthetized state. Our results show for the first time of altered temporal variance of resting state activity in anesthesia. Combined with our findings in the vegetative state, these findings suggest a close relationship between temporal variance, neural synchronization and consciousness. Hum Brain Mapp 35:5368-5378, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated resting-state abnormalities in midline regions in vegetative state/unresponsive wakefulness syndrome and minimally conscious state patients. However, the functional implications of these resting-state abnormalities remain unclear. Recent findings in healthy subjects have revealed a close overlap between the neural substrate of self-referential processing and the resting-state activity in cortical midline regions. As such, we investigated task-related neural activity during active self-referential processing and various measures of resting-state activity in 11 patients with disorders of consciousness (DOC) and 12 healthy control subjects. Overall, the results revealed that DOC patients exhibited task-specific signal changes in anterior and posterior midline regions, including the perigenual anterior cingulate cortex (PACC) and posterior cingulate cortex (PCC). However, the degree of signal change was significantly lower in DOC patients compared with that in healthy subjects. Moreover, reduced signal differentiation in the PACC predicted the degree of consciousness in DOC patients. Importantly, the same midline regions (PACC and PCC) in DOC patients also exhibited severe abnormalities in the measures of resting-state activity, that is functional connectivity and the amplitude of low-frequency fluctuations. Taken together, our results provide the first evidence of neural abnormalities in both the self-referential processing and the resting state in midline regions in DOC patients. This novel finding has important implications for clinical utility and general understanding of the relationship between the self, the resting state, and consciousness. Hum Brain Mapp 35:1997-2008, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

• A model to predict the load-carrying capacity of CLT bending-compression members were developed. • Cross layer can maintain its joint efficiency until failure. • Maximum stress of rolling shear appears at the end of beam-column. • The compression failure-based model provides good prediction of load-carrying capacity of CLT beam-columns. Rolling shear is one of the major concerns that significantly impact the performance of CLT walls if they are subjected to combined out-of-plane bending and compression loads. Because the effects of rolling shear and out-of-plane bending are coupled to each other, prediction of the load-carrying capacity of CLT wall is always a challenge for the design of CLT structures. Current design codes employ an Ayrton-Perry type interaction equation as the failure criterion to check the safety of a CLT panel loaded with combined bending and compression. Nevertheless, there is no model available to predict their load-carrying capacity. The presented work aims at developing an analytical model to predict the load-carrying capacity of CLT wall loaded with combined out-of-plane bending and compression. In total 12 five-layer CLT panels loaded with different initial load eccentricities were tested to investigate the failure modes. Observed during the test were two ultimate failure modes, i.e., compression crush on the concave side and tension rupture in convex side. Based on these failure modes and deeming the test member as a beam-column, an analytical model which takes rolling shear effects into account to predict the load-carry capacity of CLT compression-bending members was developed. An explicit formula based on compression failure mode was proposed. The model is capable of determining the distribution of rolling shear stress along longitudinal direction, rolling shear-induced axial force and moments in CLT beam-columns. By calculating the load-carrying capacities of the specimens tested in this study as well as the additional three- and seven-layer specimens tested by another studies, it was found that the compression failure mode-based formula can provide good agreements with the test results. [ABSTRACT FROM AUTHOR]

The isothermal crystallization of poly(l-lactide) (PLLA) has been investigated by in-situ wide angle X-ray diffraction (WAXD) and polarized optical microscopes (POM) equipped with a hot-stage accessory. Results showed that the spherulites of PLLA were formed at high temperature, whereas irregular morphology was observed under a low temperature. This can be attributed to the varying rates of crystallization of PLLA at different temperatures. At low temperatures, the nucleation rate is fast and hence the chains diffuse very slow, resulting in the formation of imperfect crystals. On the other hand, at high temperatures, the nucleation rate is slow and the chains diffuse fast, leading to the formation of perfect crystals. The change in the value of the Avrami exponent with temperature further verifies the varying trend in the morphological feature of the crystals. [ABSTRACT FROM AUTHOR]

Anesthetics are known to disrupt neural interactions in cortical and subcortical brain circuits. While the effect of anesthetic drugs on consciousness is reversible, the neural mechanism mediating induction and recovery may be different. Insight into these distinct mechanisms can be gained from a systematic comparison of neural dynamics during slow induction of and emergence from anesthesia. To this end, we used functional magnetic resonance imaging (fMRI) data obtained in healthy volunteers before, during, and after the administration of propofol at incrementally adjusted target concentrations. We analyzed functional connectivity of corticocortical and subcorticocortical networks and the temporal autocorrelation of fMRI signal as an index of neural processing timescales. We found that en route to unconsciousness, temporal autocorrelation across the entire brain gradually increased, whereas functional connectivity gradually decreased. In contrast, regaining consciousness was associated with an abrupt restoration of cortical but not subcortical temporal autocorrelation and an abrupt boost of subcorticocortical functional connectivity. Pharmacokinetic effects could not account for the difference in neural dynamics between induction and emergence. We conclude that the induction and recovery phases of anesthesia follow asymmetric neural dynamics. A rapid increase in the speed of cortical neural processing and subcorticocortical neural interactions may be a mechanism that reboots consciousness. [ABSTRACT FROM AUTHOR]

Achieving ultra-high thermal conductivity while maintaining the electrical insulation of polymers is highly desirable for many applications such as thermal management and packaging. In this work, polyethylene/boron nitride nanoplatelets (PE/BNNP) nanocomposite film was produced through melt processing followed by uniaxial stretching. Microstructural analysis reveals that the stretched composite film features a co-continuous network structure which consists of oriented lamellae bridged by both stretched polymer chains and aligned BNNPs along the stretching direction. The resulting film exhibit a metal-like thermal conductivity as high as 106 W m−1 K−1 and it is believed that the unique network structure has enabled efficient phonon transfer across the film, resulting in superior thermal transporting performance. This work shines a light on the design and scalable manufacturing of high performance functional polymer-based composites for future thermal management applications. [ABSTRACT FROM AUTHOR]

Determining the level of consciousness in patients with disorders of consciousness (DOC) remains challenging. To address this challenge, resting-state fMRI (rs-fMRI) has been widely used for detecting the local, regional, and network activity differences between DOC patients and healthy controls. Although substantial progress has been made towards this endeavor, the identification of robust rs-fMRI-based biomarkers for level of consciousness is still lacking. Recent developments in machine learning show promise as a tool to augment the discrimination between different states of consciousness in clinical practice. Here, we investigated whether machine learning models trained to make a binary distinction between conscious wakefulness and anesthetic-induced unconsciousness would then be capable of reliably identifying pathologically induced unconsciousness. We did so by extracting rs-fMRI-based features associated with local activity, regional homogeneity, and interregional functional activity in 44 subjects during wakefulness, light sedation, and unresponsiveness (deep sedation and general anesthesia), and subsequently using those features to train three distinct candidate machine learning classifiers: support vector machine, Extra Trees , artificial neural network. First, we show that all three classifiers achieve reliable performance within-dataset (via nested cross-validation), with a mean area under the receiver operating characteristic curve (AUC) of 0.95, 0.92, and 0.94, respectively. Additionally, we observed comparable cross-dataset performance (making predictions on the DOC data) as the anesthesia-trained classifiers demonstrated a consistent ability to discriminate between unresponsive wakefulness syndrome (UWS/VS) patients and healthy controls with mean AUC's of 0.99, 0.94, 0.98, respectively. Lastly, we explored the potential of applying the aforementioned classifiers towards discriminating intermediate states of consciousness, specifically, subjects under light anesthetic sedation and patients diagnosed as having a minimally conscious state (MCS). Our findings demonstrate that machine learning classifiers trained on rs-fMRI features derived from participants under anesthesia have potential to aid the discrimination between degrees of pathological unconsciousness in clinical patients. • Anesthetic-induced unconsciousness informs pathological unconsciousness. • Rs-fMRI-based machine learning is applied to distinguish conscious from unconscious subjects. • Machine learning models achieve reliable performance in cross-dataset generalizations. • Hyperparameter optimization significantly improves model performance. • Network-level functional connectivity features are most informative for classification. [ABSTRACT FROM AUTHOR]

The development of low‐cost and high‐performance iron (Fe)‐based anode materials is of great significance for rechargeable aqueous batteries. Herein, a FeS@Fe foam anode with crosslinked nanoflake array structure is fabricated. Being adopted as alkaline anode, FeS@Fe foam delivers enhanced areal capacity of 31.1 mAh cm−2 (at 50 mA cm−2), which is ≈1.5 times that of the‐state‐of‐the‐art literatures. The scaled‐up tests further reveal the higher capacity (800.7 mAh) and current density (1.25 A) with the area of 25 cm2. The FeS@Fe foam anode sustains intact after 270‐day cycles, demonstrating excellent durability. The assembled FeS//NiO single battery provides a superior areal energy density of 300.7 Wh m−2 at 500 W m−2. The reaction mechanism and electrode kinetics are revealed by combining in/ex situ techniques and DFT calculations. Experimental results and in/ex situ characterizations validate that excellent structural stability and high areal capacity are attributed to effective interface regulation and improved energy storage mechanism, respectively. This work pushes the advanced Fe‐based electrode to a superior level among these available alkaline solid‐state batteries. [ABSTRACT FROM AUTHOR]

Global warming has emerged as a serious threat to humans and sustainable development. China is under increasing pressure to curb its carbon emissions as the world's largest emitter of carbon dioxide. By combining the Tapio decoupling model and the environmental Kuznets curve (EKC) framework, this paper explores the relationship between China's carbon emissions and economic growth. Based on panel data of 29 provinces from 2007 to 2016, this paper quantitatively estimates the nexus of carbon emissions and economic development for the whole nation and the decoupling status of individual provinces. There is empirical evidence for the conventional EKC hypothesis, showing that the relationship between carbon emissions and per capita gross domestic product (GDP) is an inverted U shape and that the inflection point will not be attained soon. Moreover, following the estimation results of the Tapio decoupling model, there were significant differences between individual provinces in decoupling status. As a result, differentiated and targeted environmental regulations and policies regarding energy consumption and carbon emissions should be reasonably formulated for different provinces and regions based on the corresponding level of economic development and decoupling status. [ABSTRACT FROM AUTHOR]

Theoretical consideration predicts that the alteration of local and shared information in the brain is a key element in the mechanism of anesthetic-induced unconsciousness. Ordinal pattern analysis, such as permutation entropy (PE) and symbolic mutual information (SMI), have been successful in quantifying local and shared information in neurophysiological data; however, they have been rarely applied to altered states of consciousness, especially to data obtained with functional magnetic resonance imaging (fMRI). PE and SMI analysis, together with the superb spatial resolution of fMRI recording, enables us to explore the local information of specific brain areas, the shared information between the areas, and the relationship between the two. Given the spatially divergent action of anesthetics on regional brain activity, we hypothesized that anesthesia would differentially influence entropy (PE) and shared information (SMI) across various brain areas, which may represent fundamental, mechanistic indicators of loss of consciousness. FMRI data were collected from 15 healthy participants during four states: wakefulness (W), light (conscious) sedation (L), deep (unconscious) sedation (D), and recovery (R). Sedation was produced by the common, clinically used anesthetic, propofol. Firstly, we found that that global PE decreased from W to D, and increased from D to R. The PE was differentially affected across the brain areas; specifically, the PE in the subcortical network was reduced more than in the cortical networks. Secondly, SMI was also differentially affected in different areas, as revealed by the reconfiguration of its spatial pattern (topographic structure). The topographic structures of SMI in the conscious states W, L, and R were distinctively different from that of the unconscious state D. Thirdly, PE and SMI were positively correlated in W, L, and R, whereas this correlation was disrupted in D. And lastly, PE changes occurred preferentially in highly connected hub regions. These findings advance our understanding of brain dynamics and information exchange, emphasizing the importance of topographic structure and the relationship of local and shared information in anesthetic-induced unconsciousness. [ABSTRACT FROM AUTHOR]

Smoke exposure during pregnancy has detrimental effects upon numerous fetal and neonatal outcomes. Nicotine (the main component of tobacco) has been suggested to affect placental development. During placental development, efficient invasion by trophoblasts is required for establishment of the fetus–maternal circulation. In this study we explored the regulation of trophoblast invasion by nicotine. An immortalized first trimester extravillous trophoblast cell line (HTR-8/SVneo cells) was used for all the experiments, which were treated by nicotine, methyllycaconitine, and C-X-C motif chemokine ligand 12 (CXCL12). Total RNA and protein were used to study the expressions of nicotinic acetylcholine receptors (nAChRs), and transwell assay was used to study invasiveness. Changes of RNA expression due to nicotine treatment were detected by RNA sequence. Level of CXCL12 mRNA was verified by quantitative PCR. We showed that HTR-8/SVneo expressed subunits α2–4, α7, α9, β1, and β2 of nAChRs. Nicotine downregulated CXCL12 expression and inhibited trophoblast invasion. Methyllycaconitine, as an antagonist of the α7 homopolymer, blocked the inhibitory effect of nicotine. CXCL12 could rescue the nicotine-induced inhibitory effect on invasion of HTR-8/SVneo cells. These results suggest that the α7 subunit of the nAChR has important roles in modulating trophoblast invasion through CXCL12. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor- (CAR-) T cell therapy is one of the most recent innovative immunotherapies and is rapidly evolving. Like other technologies, CAR-T cell therapy has undergone a long development process, and persistent explorations of the actions of the intracellular signaling domain and make several improvements have led to the superior efficacy when anti-CD19 CAR-T cell treatments in B cell cancers. At present, CAR-T cell therapy is developing rapidly, and many clinical trials have been established on a global scale, which has great commercial potential. This review mainly describes the toxicity of CAR-T cell therapy and the challenges of CAR-T cells in the treatment of solid tumors, and looks forward to future development and opportunities for immunotherapy and reviews major breakthroughs in CAR-T cell therapy. [ABSTRACT FROM AUTHOR]

Background and Objectives: Advanced esophageal squamous cell carcinoma (ESCC) is a prevalent and highly malignant tumor with a poor prognosis. Recently, the RATIONALE-306 trial demonstrated that tislelizumab combined with chemotherapy provided overall survival benefits for these patients. This study aimed to assess the cost-effectiveness of this treatment approach in Chinese patients with advanced ESCC from the perspective of healthcare system. Methods: A Markov model was constructed to assess the economic and health benefits associated with tislelizumab plus chemotherapy over a 10-year lifetime horizon, utilizing data from the RATIONALE-306 trial. The analysis encompassed the calculation of several key parameters, including the incremental cost-effectiveness ratio (ICER), total cost, incremental cost, total effectiveness, and incremental effectiveness. Tislelizumab was considered cost-effective if the ICER obtained was below the willingness-to-pay (WTP) threshold of US$38,223 per quality-adjusted life-year (QALY); otherwise, it would be deemed not cost-effective. To ensure the robustness of the findings, the results were subjected to one-way sensitivity analysis and probabilistic sensitivity analysis (PSA). Results: In the base-case analysis, the incremental effectiveness and cost associated with tislelizumab plus chemotherapy, compared to chemotherapy alone, were determined to be 0.40 QALY and US$7604, respectively. This resulted in an ICER of US$18,846 per QALY, which is below the WTP threshold of US$38,223 per QALY. Furthermore, the results from the one-way sensitivity analysis and PSA indicated robustness of the findings. Conclusion: Our lifetime simulation study demonstrated that, in the case of advanced ESCC, the combination of tislelizumab and chemotherapy offers increased effectiveness compared to chemotherapy alone, albeit at a higher cost. Moreover, considering the current WTP threshold in China, the addition of tislelizumab to chemotherapy is considered a cost-effective approach. [ABSTRACT FROM AUTHOR]

Abstract Background Despite the great number of resting state functional connectivity studies on Eating Disorders (ED), no biomarkers could be detected yet. Therefore, we here focus on a different measure of resting state activity that is neuronal variability. The objective of this study was to investigate neuronal variability in the resting state of women with ED and to correlate possible differences with clinical and psychopathological indices. Methods 58 women respectively 25 with Anorexia Nervosa (AN), 16 with Bulimia Nervosa (BN) and 17 matched healthy controls (CN) were enrolled for the study. All participants were tested with a battery of psychometric tests and underwent a functional Magnetic Resonance Imaging (fMRI) resting state scanning. We investigated topographical patterns of variability measured by the Standard Deviation (SD) of the Blood-Oxygen-Level-Dependent (BOLD) signal (as a measure of neuronal variability) in the resting-state and their relationship to clinical and psychopathological indices. Results Neuronal variability was increased in both anorectic and bulimic subjects specifically in the Ventral Attention Network (VAN) compared to healthy controls. No significant differences were found in the other networks. Significant correlations were found between neuronal variability of VAN and various clinical and psychopathological indices. Conclusions We here show increased neuronal variability of VAN in ED patients. As the VAN is relevant for switching between endogenous and exogenous stimuli, our results showing increased neuronal variability suggest unstable balance between body attention and attention to external world. These results offer new perspective on the neurobiological basis of ED. Clinical and therapeutic implication will be discussed. [ABSTRACT FROM AUTHOR]

• Classical and non-classical psychedelics induce common brain network changes. • Nitrous oxide, ketamine, and LSD all reduce within-network connectivity. • Nitrous oxide, ketamine, and LSD all enhance between-network connectivity. • Changes in temporoparietal junction are consistent across diverse psychedelics. The neurobiology of the psychedelic experience is not fully understood. Identifying common brain network changes induced by both classical (i.e., acting at the 5-HT 2 receptor) and non-classical psychedelics would provide mechanistic insight into state-specific characteristics. We analyzed whole-brain functional connectivity based on resting-state fMRI data in humans, acquired before and during the administration of nitrous oxide, ketamine, and lysergic acid diethylamide. We report that, despite distinct molecular mechanisms and modes of delivery, all three psychedelics reduced within-network functional connectivity and enhanced between-network functional connectivity. More specifically, all three drugs increased connectivity between right temporoparietal junction and bilateral intraparietal sulcus as well as between precuneus and left intraparietal sulcus. These regions fall within the posterior cortical "hot zone," posited to mediate the qualitative aspects of experience. Thus, both classical and non-classical psychedelics modulate networks within an area of known relevance for consciousness, identifying a biologically plausible candidate for their subjective effects. [ABSTRACT FROM AUTHOR]

Complete locked-in syndrome (CLIS) resulting from late-stage amyotrophic lateral sclerosis (ALS) is characterised by loss of motor function and eye movements. The absence of behavioural indicators of consciousness makes the search for neuronal correlates as possible biomarkers clinically and ethically urgent. EEG-based measures of brain dynamics such as power-law exponent (PLE) and Lempel-Ziv complexity (LZC) have been shown to have explanatory power for consciousness and may provide such neuronal indices for patients with CLIS. Here, we validated PLE and LZC (calculated in a dynamic way) as benchmarks of a wide range of arousal states across different reference states of consciousness (e.g., awake, sleep stages, ketamine, sevoflurane). We show a tendency toward high PLE and low LZC, with high intra-subject fluctuations and inter-subject variability in a cohort of CLIS patients with values graded along different arousal states as in our reference data sets. In conclusion, changes in brain dynamics indicate altered arousal in CLIS. Specifically, PLE and LZC are potentially relevant biomarkers to identify or diagnose the arousal level in CLIS and to determine the optimal time point for treatment, including communication attempts. EEG-based dynamics associated with different arousal states are used to identify indices associated with complete locked-in syndrome, which could aid treatments and communication aids [ABSTRACT FROM AUTHOR]

Simple Summary: Intrinsic immunogenic cell death (ICD) property plays an important role in the prognosis and immune microenvironment of patients with lung adenocarcinoma (LUAD). In this study, we performed an overall multi-omics analysis of the intrinsic ICD property and developed a risk scoring system. We found two distinct ICD-associated transcriptomic molecular patterns (termed ICD-high and ICD-low). We identified and validated ICDrisk subtypes (ICDrisk) which can effectively predict overall survival (OS) in LUAD patients and immunotherapeutic response across Pan-cancer. Our results may help to elucidate the underlying molecular mechanisms of intrinsic immunogenicity and heterogeneous responses to immunotherapy in LUAD patients. Recent studies have highlighted the combination of activation of host immunogenic cell death (ICD) and tumor-directed cytotoxic strategies. However, overall multiomic analysis of the intrinsic ICD property in lung adenocarcinoma (LUAD) has not been performed. Therefore, the aim of this study was to develop an ICD-based risk scoring system to predict overall survival (OS) and immunotherapeutic efficacy in patients. In our study, both weighted gene co-expression network analysis (WGCNA) and LASSO-Cox analysis were utilized to identify ICDrisk subtypes (ICDrisk). Moreover, we identify genomic alterations and differences in biological processes, analyze the immune microenvironment, and predict the response to immunotherapy in patients with pan-cancer. Importantly, immunogenicity subgroup typing was performed based on the immune score (IS) and microenvironmental tumor neoantigens (meTNAs). Our results demonstrate that ICDrisk subtypes were identified based on 16 genes. Furthermore, high ICDrisk was proved to be a poor prognostic factor in LUAD patients and indicated poor efficacy of immune checkpoint inhibitor (ICI) treatment in patients with pan-cancer. The two ICDrisk subtypes displayed distinct clinicopathologic features, tumor-infiltrating immune cell patterns, and biological processes. The ISlowmeTNAhigh subtype showed low intratumoral heterogeneity (ITH) and immune-activated phenotypes and correlated with better survival than the other subtypes within the high ICDrisk group. This study suggests effective biomarkers for the prediction of OS in LUAD patients and immunotherapeutic response across Pan-cancer and contributes to enhancing our understanding of intrinsic immunogenic tumor cell death. [ABSTRACT FROM AUTHOR]

Scale-free physiological processes are ubiquitous in the human organism. Resting-state functional MRI studies observed the loss of scale-free dynamics under anesthesia. In contrast, the modulation of scale-free dynamics during task-related activity remains an open question. We investigate scale-free dynamics in the cerebral cortex's unimodal periphery and transmodal core topography in rest and task states during three conscious levels (awake, sedation, and anesthesia) complemented by computational modelling (Stuart-Landau model). The empirical findings demonstrate that the loss of the brain's intrinsic scale-free dynamics in the core-periphery topography during anesthesia, where pink noise transforms into white noise, disrupts the brain's neuronal alignment with the task's temporal structure. The computational model shows that the stimuli's scale-free dynamics, namely pink noise distinguishes from brown and white noise, also modulate task-related activity. Together, we provide evidence for two mechanisms of consciousness, temporo-spatial nestedness and alignment, suggested by the Temporo-Spatial Theory of Consciousness (TTC). Summary: Investigation of scale-free brain dynamics via rest-task modulation across awake, sedative, and anesthetic states of consciousness shows that brain dynamics lose alignment to the task's temporal structure in anesthesia as in wakefulness. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigated the effect and mechanism of zinc-finger protein 418 (ZNF418) on cardiac hypertrophy caused by aortic banding (AB), phenylephrine (PE) or angiotensin II (Ang II) in vivo and in vitro. Methods: The expression of ZNF418 in hearts of patients with dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM) and AB-induced cardiac hypertrophy mice, as well as in Ang II- or PE-induced hypertrophic primary cardiomyocytes was detected by western blotting. Then, the expression of ZNF418 was up-regulated or down-regulated in AB-induced cardiac hypertrophy mice and Ang II -induced hypertrophic primary cardiomyocytes. The hypertrophic responses and fibrosis were evaluated by echocardiography and histological analysis. The mRNA levels of hypertrophy markers and fibrotic markers were detected by RT-qPCR. Furthermore, the phosphorylation and total levels of c-Jun were measured by western blotting. Results: ZNF418 was markedly down-regulated in hearts of cardiac hypertrophy and hypertrophic primary cardiomyocytes. Down-regulated ZNF418 exacerbated the myocyte size and fibrosis, moreover increased the mRNA levels of ANP, BNP, β-MHC, MCIP1.4, collagen 1a, collagen III, MMP-2 and fibronection in hearts of AB-treated ZNF418 knockout mice or Ang II-treated cardiomyocytes with AdshZNF418. Conversely, these hypertrophic responses were reduced in the ZNF418 transgenic (TG) mice treated by AB and the AdZNF418-transfected primary cardiomyocytes treated by Ang II. Additionally, the deficiency of ZNF418 enhanced the phosphorylation level of c-jun, and overexpression of ZNF418 suppressed the phosphorylation level of c-jun in vivo and in vitro. Conclusion: ZNF418 maybe attenuate hypertrophic responses by inhibiting the activity of c-jun/AP-1. [ABSTRACT FROM AUTHOR]

The human brain's cerebral cortex exhibits a topographic division into higher‐order transmodal core and lower‐order unimodal periphery regions. While timescales between the core and periphery region diverge, features of their power spectra, especially scale‐free dynamics during resting‐state and their mdulation in task states, remain unclear. To answer this question, we investigated the ~1/f‐like pink noise manifestation of scale‐free dynamics in the core‐periphery topography during rest and task states applying infra‐slow inter‐trial intervals up to 1 min falling inside the BOLD's infra‐slow frequency band. The results demonstrate (1) higher resting‐state power‐law exponent (PLE) in the core compared to the periphery region; (2) significant PLE increases in task across the core and periphery regions; and (3) task‐related PLE increases likely followed the task's atypically low event rates, namely the task's periodicity (inter‐trial interval = 52–60 s; 0.016–0.019 Hz). A computational model and a replication dataset that used similar infra‐slow inter‐trial intervals provide further support for our main findings. Altogether, the results show that scale‐free dynamics differentiate core and periphery regions in the resting‐state and mediate task‐related effects. [ABSTRACT FROM AUTHOR]

• Fabricated a grinding tool for coronary calcified tissue removal. • Analyzed the force, temperature and debris morphology during the grinding process. • Illustrated the influence of tool parameters and grinding parameters on grinding results. Coronary rotational atherectomy (CRA) means of use a tiny grinding tool to rotate at high speed in the blood vessels, so as to remove calcified tissue, effectively enlarge the inner diameter of the vessels, which is an important tool for the treatment of cardiovascular calcified blockage. However, excessive grinding force, temperature and debris size can lead to serious surgical complications and endanger the patient life during CRA. This study introduces the design, fabrication and performance verification process of a novel grinding tool, and investigates the influence of tool geometrical parameters and grinding parameters The experimental results showed that: the novel grinding tool can effectively remove the simulated calcified tissue by grinding. The geometrical size of tools plays an important effect on the grinding properties, which can result in increasing grinding force, temperature and debris size with the increase of tool diameters. In addition, with the increase of rotational speed, the grinding force and temperature increase gradually, while the debris size decreases as the rotational speed increases. The increasing inner diameter of bone can also lead to a decrease in grinding force and temperature slightly. All the obtained results can give effective guidance for clinical operations. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate the roles of different resting-state networks in predicting both the actual level of consciousness and its recovery in brain injury patients.Methods: We investigated resting-state functional connectivity within different networks in patients with varying levels of consciousness: unresponsive wakefulness syndrome (UWS; n = 56), minimally conscious state (MCS; n = 29), and patients with brain lesions but full consciousness (BL; n = 48). Considering the actual level of consciousness, we compared the strength of network connectivity among the patient groups. We then checked the presence of connections between specific regions in individual patients and calculated the frequency of this in the different patient groups. Considering the recovery of consciousness, we split the UWS group into 2 subgroups according to recovery: those who emerged from UWS (UWS-E) and those who remained in UWS (UWS-R). The above analyses were repeated on these 2 subgroups.Results: Functional connectivity strength in salience network (SN), especially connectivity between the supragenual anterior cingulate cortex (SACC) and left anterior insula (LAI), was reduced in the unconscious state (UWS) compared to the conscious state (MCS and BL). Moreover, at the individual level, SACC-LAI connectivity was more present in MCS than in UWS. Default-mode network (DMN) connectivity strength, especially between the posterior cingulate cortex (PCC) and left lateral parietal cortex (LLPC), was reduced in UWS-R compared with UWS-E. Furthermore, PCC-LLPC connectivity was more present in UWS-E than in UWS-R.Interpretation: Our findings show that SN (SACC-LAI) connectivity correlates with behavioral signs of consciousness, whereas DMN (PCC-LLPC) connectivity instead predicts recovery of consciousness. [ABSTRACT FROM AUTHOR]

Stroke is a complex event on both behavioral and neuronal grounds. Recent investigations evidence the central role of subcortical damage on the post-stroke brain and behavior reorganization. We have conducted an exploratory study combining anatomical lesion analysis, functional analysis of resting state fMRI, and behavioral assessment with focus on exploration as represented by SEEKING. 24 stroke inpatients were studied immediately after their clinical stabilization post-stroke; neuronal variability in fMRI along with behavioral outcomes were assessed. These outcomes were compared with a control group of 22 healthy subjects. First, we observed predominant subcortical lesions in our sample with all stroke patients showing subcortical lesions and only some exhibiting additional cortical lesions. Second, we observed significantly reduced neuronal variability in the posterior cingulate cortex (PCC) that did not show any structural damage. Third, our stroke subjects showed reduced SEEKING which was related to reduced PCC neuronal variability in an abnormal way (compared to healthy subjects). This last outcome was assessed by considering the subset of 11 stroke subjects for which fMRI and behavioral outcomes were jointly measured. Taken together, our findings suggest that damage in subcortical regions may play a central role in abnormalities in both cortical activity (PCC) and associated behavior of post-stroke reorganization. Accounting for these aspects may have significant implications to optimize multidisciplinary rehabilitation processes, particularly during the early steps of recovery, reducing the impact of stroke on the patient and caregiver quality of life. [ABSTRACT FROM AUTHOR]

Due to an error in production, the article should have indicated that Jing Chen and Min Qiu are co-first authors, as displayed here. [ABSTRACT FROM AUTHOR]

MicroRNAs(miRNAs) are maladjusted in multifarious malignant tumor and can be considered as both carcinogens and tumor‐inhibiting factor. In the present study, we analyzed the miRNAs expression profiles and clinical information of 481 patients with head and neck squamous cell carcinoma (HNSCC) through the TCGA dataset to identify the prognostic miRNAs signature. A total of 114 significantly differentially expressed miRNAs (SDEMs) were identified, consisting of 60 up‐adjusted and 54 down‐adjusted miRNAs. The Kaplan‐Meier survival method identified the prognostic function of 2 miRNAs (miR‐4652‐5p and miR‐99a‐3P). Univariate and multivariate Cox regression analyses indicated that the 2 miRNAs were significant prognostic elements of HNSCC. Furthermore, bioinformatic analysis was conducted by means of 4 online gene predicted toolkits to recognize the target genes, and enrichment analysis was performed on the target genes by DAVID. The outcomes depicted that target genes were correlated with calcium, as well as cell proliferation, circadian entrainment, EGFR, PI3K‐Akt‐mTOR, and P53 signaling pathways. Finally, the PPI network was conducted in view of STRING database and Cytoscape. Eight hub genes were identified by CytoHubba and MCODE app, respectively, CBL, SKP1, H2AFX, HGF, POLR2F, UBE2I, VAMP2, and GNAI2 genes. As a result, we identified 2 miRNAs signatures, 8 hub genes, and significant signaling pathways for estimating the prognosis of HNSCC. In order to further explore the molecular mechanism of HNSCC occurrence and development, more comprehensive basic and clinical studies are needed. [ABSTRACT FROM AUTHOR]

The self is the core of our mental life. Previous investigations have demonstrated a strong neural overlap between self‐related activity and resting state activity. This suggests that information about self‐relatedness is encoded in our brain's spontaneous activity. The exact neuronal mechanisms of such "rest‐self containment," however, remain unclear. The present EEG study investigated temporal measures of resting state EEG to relate them to self‐consciousness. This was obtained with the self‐consciousness scale (SCS) which measures Private, Public, and Social dimensions of self. We demonstrate positive correlations between Private self‐consciousness and three temporal measures of resting state activity: scale‐free activity as indexed by the power‐law exponent (PLE), the auto‐correlation window (ACW), and modulation index (MI). Specifically, higher PLE, longer ACW, and stronger MI were related to higher degrees of Private self‐consciousness. Finally, conducting eLORETA for spatial tomography, we found significant correlation of Private self‐consciousness with activity in cortical midline structures such as the perigenual anterior cingulate cortex and posterior cingulate cortex. These results were reinforced with a data‐driven analysis; a machine learning algorithm accurately predicted an individual as having a "high" or "low" Private self‐consciousness score based on these measures of the brain's spatiotemporal structure. In conclusion, our results demonstrate that Private self‐consciousness is related to the temporal structure of resting state activity as featured by temporal nestedness (PLE), temporal continuity (ACW), and temporal integration (MI). Our results support the hypothesis that self‐related information is temporally contained in the brain's resting state. "Rest‐self containment" can thus be featured by a temporal signature. [ABSTRACT FROM AUTHOR]

Neural activity varies continually from moment to moment. Such temporal variability (TV) has been highlighted as a functionally specific brain property playing a fundamental role in cognition. We sought to investigate the mechanisms involved in TV changes between two basic behavioral states, namely having the eyes open (EO) or eyes closed (EC) in vivo in humans. To these ends we acquired BOLD fMRI, ASL, and [ 18 F]-fluoro-deoxyglucose PET in a group of healthy participants ( n  = 15), along with BOLD fMRI and [ 18 F]-flumazenil PET in a separate group ( n  = 19). Focusing on an EO- vs EC-sensitive region in the occipital cortex (identified in an independent sample), we show that TV is constrained in the EO condition compared to EC. This reduction is correlated with an increase in energy consumption and with regional GABA A receptor density. This suggests that the modulation of TV by behavioral state involves an increase in overall neural activity that is related to an increased effect from GABAergic inhibition in addition to any excitatory changes. These findings contribute to our understanding of the mechanisms underlying activity variability in the human brain and its control. [ABSTRACT FROM AUTHOR]