Substantia Innominata Glutamatergic Neurons Modulate Sevoflurane Anesthesia in Male Mice.

BACKGROUND: Accumulated evidence suggests that brain regions that promote wakefulness also facilitate emergence from general anesthesia (GA). Glutamatergic neurons in the substantia innominata (SI) regulate motivation-related aversive, depressive, and aggressive behaviors relying on heightened arousal. Here, we hypothesize that glutamatergic neurons in the SI are also involved in the regulation of the effects of sevoflurane anesthesia. METHODS: With a combination of fiber photometry, chemogenetic and optogenetic tools, behavioral tests, and cortical electroencephalogram recordings, we investigated whether and how SI glutamatergic neurons and their projections to the lateral hypothalamus (LH) regulate sevoflurane anesthesia in adult male mice. RESULTS: Population activity of glutamatergic neurons in the SI gradually decreased upon sevoflurane-induced loss of consciousness (LOC) and slowly returned as soon as inhalation of sevoflurane discontinued before recovery of consciousness (ROC). Chemogenetic activation of SI glutamatergic neurons dampened the animals' sensitivity to sevoflurane exposure, prolonged induction time (mean ± standard deviation [SD]; 389 ± 67 seconds vs 458 ± 53 seconds; P = .047), and shortened emergence time (305 seconds, 95% confidence interval [CI], 242-369 seconds vs 207 seconds, 95% CI, 135-279 seconds; P = .004), whereas chemogenetic inhibition of these neurons facilitated sevoflurane anesthesia. Furthermore, optogenetic activation of SI glutamatergic neurons and their terminals in LH induced cortical activation and behavioral emergence from different depths of sevoflurane anesthesia. CONCLUSIONS: Our study shows that SI glutamatergic neuronal activity facilitates emergence from sevoflurane anesthesia and provides evidence for the involvement of the SI-LH glutamatergic pathway in the regulation of consciousness during GA.

DNA-based ForceChrono probes for deciphering single-molecule force dynamics in living cells.

Understanding cellular force transmission dynamics is crucial in mechanobiology. We developed the DNA-based ForceChrono probe to measure force magnitude, duration, and loading rates at the single-molecule level within living cells. The ForceChrono probe circumvents the limitations of in vitro single-molecule force spectroscopy by enabling direct measurements within the dynamic cellular environment. Our findings reveal integrin force loading rates of 0.5-2 pN/s and durations ranging from tens of seconds in nascent adhesions to approximately 100 s in mature focal adhesions. The probe's robust and reversible design allows for continuous monitoring of these dynamic changes as cells undergo morphological transformations. Additionally, by analyzing how mutations, deletions, or pharmacological interventions affect these parameters, we can deduce the functional roles of specific proteins or domains in cellular mechanotransduction. The ForceChrono probe provides detailed insights into the dynamics of mechanical forces, advancing our understanding of cellular mechanics and the molecular mechanisms of mechanotransduction.

Vehicle Occupant Detection Based on MM-Wave Radar.

With the continuous development of automotive intelligence, vehicle occupant detection technology has received increasing attention. Despite various types of research in this field, a simple, reliable, and highly private detection method is lacking. This paper proposes a method for vehicle occupant detection using millimeter-wave radar. Specifically, the paper outlines the system design for vehicle occupant detection using millimeter-wave radar. By collecting the raw signals of FMCW radar and applying Range-FFT and DoA estimation algorithms, a range-azimuth heatmap was generated, visually depicting the current status of people inside the vehicle. Furthermore, utilizing the collected range-azimuth heatmap of passengers, this paper integrates the Faster R-CNN deep learning networks with radar signal processing to identify passenger information. Finally, to test the performance of the detection method proposed in this article, an experimental verification was conducted in a car and the results were compared with those of traditional machine learning algorithms. The findings indicated that the method employed in this experiment achieves higher accuracy, reaching approximately 99%.

Distance and grid-like codes support the navigation of abstract social space in the human brain.

People form impressions about others during daily social encounters and infer personality traits from others' behaviors. Such trait inference is thought to rely on two universal dimensions: competence and warmth. These two dimensions can be used to construct a 'social cognitive map' organizing massive information obtained from social encounters efficiently. Originating from spatial cognition, the neural codes supporting the representation and navigation of spatial cognitive maps have been widely studied. Recent studies suggest similar neural mechanism subserves the map-like architecture in social cognition as well. Here we investigated how spatial codes operate beyond the physical environment and support the representation and navigation of social cognitive map. We designed a social value space defined by two dimensions of competence and warmth. Behaviorally, participants were able to navigate to a learned location from random starting locations in this abstract social space. At the neural level, we identified the representation of distance in the precuneus, fusiform gyrus, and middle occipital gyrus. We also found partial evidence of grid-like representation patterns in the medial prefrontal cortex and entorhinal cortex. Moreover, the intensity of grid-like response scaled with the performance of navigating in social space and social avoidance trait scores. Our findings suggest a neurocognitive mechanism by which social information can be organized into a structured representation, namely cognitive map and its relevance to social well-being.

Leisure activities as reserve mediators of the relationship between loneliness and cognition in aging.

Previous studies have found that loneliness affects cognitive functions in older persons. However, the influence of loneliness on different cognitive fields and the internal mechanism of the relationship are unclear. A total of 4772 older persons aged above 50 years (Mean = 65.31, SD = 6.96, 57.7% female) were included in this study. All the participants completed the characteristics scale, as well as the loneliness scale, leisure activity scale, and cognitive function tests in six domains. The results showed that 17.6% of participants had high loneliness, while 16.7% of participants had low loneliness. Associations were observed between higher levels of loneliness and lower scores in general cognitive ability, memory, and executive functions. Mediation analysis suggested that leisure activities, encompassing mental, physical, and social activities, were associated with cognitive functions in the context of loneliness. These results indicate that leisure activities may play a significant role in the relationship between loneliness and cognitive functions in older adults. The study highlights the importance of considering leisure activities in this demographic to potentially mitigate the adverse cognitive effects associated with loneliness.

Clathrin light chains negatively regulate plant immunity by hijacking the autophagy pathway.

The crosstalk between clathrin-mediated endocytosis (CME) and the autophagy pathway has been reported in mammals; however, the interconnection of CME with autophagy has not been established in plants. Here, we report that the Arabidopsis CLATHRIN LIGHT CHAIN (CLC) subunit 2 and 3 double mutant, clc2-1 clc3-1, phenocopies Arabidopsis AUTOPHAGY-RELATED GENE (ATG) mutants in both autoimmunity and nutrient sensitivity. Accordingly, the autophagy pathway is significantly compromised in the clc2-1 clc3-1 mutant. Interestingly, multiple assays demonstrate that CLC2 directly interacts with ATG8h/ATG8i in a domain-specific manner. As expected, both GFP-ATG8h/GFP-ATG8i and CLC2-GFP are subjected to autophagic degradation, and degradation of GFP-ATG8h is significantly reduced in the clc2-1 clc3-1 mutant. Notably, simultaneous knockout of ATG8h and ATG8i by CRISPR-Cas9 results in enhanced resistance against Golovinomyces cichoracearum, supporting the functional relevance of the CLC2-ATG8h/8i interactions. In conclusion, our results reveal a link between the function of CLCs and the autophagy pathway in Arabidopsis.

Machine Learning Assisted Self-Powered Identity Recognition Based on Thermogalvanic Hydrogel for Intelligent Security.

Identity recognition as the first barrier of intelligent security plays a vital role, which is facing new challenges that are unable to meet the need of intelligent era due to low accuracy, complex configuration and dependence on power supply. Here, a finger temperature-driven intelligent identity recognition strategy is presented based on a thermogalvanic hydrogel (TGH) by actively discerning biometric characteristics of fingers. The TGH is a dual network PVA/Agar hydrogel in an H2O/glycerol binary solvent with [Fe(CN)6]3-/4- as a redox couple. Using a concave-arranged TGH array, the characteristics of users can be distinguished adequately even under an open environment by extracting self-existent intrinsic temperature features from five typical sites of fingers. Combined with machine learning, the TGH array can recognize different users with a high average accuracy of 97.6%. This self-powered identity recognition strategy is further applied to a smart lock, attaining a more reliable security protection from biometric characteristics than bare passwords. This work provides a promising solution for achieving better identity recognition, which has great advantages in intelligent security and human-machine interaction toward future Internet of everything.

[GmAGB1 plays a positive regulatory role in soybean defense responses].

Heterotrimeric GTP-binding protein (G-proteins) complex, which consists of Gα, Gß and Gγ subunits, plays critical roles in defense signaling. Arabidopsis genome contains only a single Gß-encoding gene, AGB1. Loss function of AGB1 in Arabidopsis results in enhanced susceptibility to a wide range of pathogens. However, the function of soybean AGB1 in immunity has not been previously interrogated. Bioinformatic analysis indicated that there are four GmAGB1 homologous genes in soybean genome, sharing homology of 86%-97%. To overcome the functional redundancy of these GmAGB1 homologs, virus-induced gene silencing (VIGS) mediated by the bean pod mottle virus (BPMV) was used to silence these four genes simultaneously. As expected, these four GmAGB1 homologous genes were indeed silenced by a single BPMV-VIGS vector carrying a conserved fragments among these four genes. A dwarfed phenotype was observed in GmAGB1s-silenced soybean plants, suggesting that GmAGB1s play a crucial role in growth and development. Disease resistance analysis indicated that silencing GmAGB1s significantly compromised the resistance of soybean plants against Xanthomonas campestris pv. glycinea (Xag). This reduced resistance was correlated with the decreased accumulation of pathogen-induced reactive oxygen species (ROS) and the reduced activation of GmMPK3 in response to flg22, a conserved N-terminal peptide of flagellin protein. These results indicate that GmAGB1 functions as a positive regulator in disease resistance and GmAGB1 is indispensable for the ROS production and GmMPK3 activation induced by pathogen infection. Yeast two hybrid assay showed that GmAGB1 interacted with GmAGG1, suggesting that an evolutionary conserved heterotrimeric G protein complex similarly functions in soybean.

[Silencing GmWRKY33B genes leads to reduced disease resistance in soybean].

The WRKYs are a group of plant-specific transcription factors that play important roles in defense responses. In this study, we silenced 2 GmWRKY33B homologous genes using a bean pod mosaic virus (BPMV) vector carrying a single fragment from the conserved region of the GmWRKY33B genes. Silencing GmWRKY33B did not result in morphological changes. However, significantly reduced resistances to Pseudomonas syringae pv. glycinea (Psg) and soybean mosaic virus (SMV) were observed in the GmWRKY33B-silenced plants, indicating a positive role of the GmWRKY33B genes in disease resistance. Kinase assay showed that silencing the GmWRKY33B genes significantly reduced the activation of GmMPK6, but not GmMPK3, in response to flg22 treatment. Reverse transcriptase PCR (RT-PCR) analysis of the genes encoding prenyltransferases (PTs), which are the key enzymes in the biosynthesis of glyceollin, showed that the Psg-induced expression of these genes was significantly reduced in the GmWRKY33B-silenced plants compared with the BPMV-0 empty vector plants, which correlated with the presence of the W-boxes in the promoter regions of these genes. Taken together, our results suggest that GmWRKY33Bs are involved in soybean immunity through regulating the activation of the kinase activity of GmMPK6 as well as through regulating the expression of the key genes encoding the biosynthesis of glyceollins.

Graph embedding-based heterogeneous domain adaptation with domain-invariant feature learning and distributional order preserving.

Heterogeneous domain adaptation (HDA) methods leverage prior knowledge from the source domain to train models for the target domain and address the differences in their feature spaces. However, incorrect alignment of categories and distribution structure disruption may be caused by unlabeled target samples during the domain alignment process for most existing methods, resulting in negative transfer. Additionally, the previous works rarely focus on the robustness and interpretability of the model. To address these issues, we propose a novel Graph embedding-based Heterogeneous domain-Invariant feature learning and Distributional order preserving framework (GHID). Specifically, a bidirectional robust cross-domain alignment graph embedding structure is proposed to globally align two domains, which learns the domain-invariant and discriminative features simultaneously. In addition, the interpretability of the proposed graph structures is demonstrated through two theoretical analyses, which can elucidate the correlation between important samples from a global perspective in heterogeneous domain alignment scenarios. Then, a heterogeneous discriminative distributional order preserving graph embedding structure is designed to preserve the original distribution relationship of each domain to prevent negative transfer. Moreover, the dynamic centroid strategy is incorporated into the graph structures to improve the robustness of the model. Comprehensive experimental results on four benchmarks demonstrate that the proposed method outperforms other state-of-the-art approaches in effectiveness.

Silencing GmATG7 Leads to Accelerated Senescence and Enhanced Disease Resistance in Soybean.

Autophagy plays a critical role in nutrient recycling/re-utilizing under nutrient deprivation conditions. However, the role of autophagy in soybeans has not been intensively investigated. In this study, the Autophay-related gene 7 (ATG7) gene in soybeans (referred to as GmATG7) was silenced using a virus-induced gene silencing approach mediated by Bean pod mottle virus (BPMV). Our results showed that ATG8 proteins were highly accumulated in the dark-treated leaves of the GmATG7-silenced plants relative to the vector control leaves (BPMV-0), which is indicative of an impaired autophagy pathway. Consistent with the impaired autophagy, the dark-treated GmATG7-silenced leaves displayed an accelerated senescence phenotype, which was not seen on the dark-treated BPMV-0 leaves. In addition, the accumulation levels of both H2O2 and salicylic acid (SA) were significantly induced in the GmATG7-silenced plants compared with the BPMV-0 plants, indicating an activated immunity. Consistently, the GmATG7-silenced plants were more resistant against both Pseudomonas syringae pv. glycinea (Psg) and Soybean mosaic virus (SMV) compared with the BPMV-0 plants. However, the activated immunity in the GmATG7-silenced plant was not dependent upon the activation of MPK3/MPK6. Collectively, our results demonstrated that the function of GmATG7 is indispensable for autophagy in soybeans, and the activated immunity in the GmATG7-silenced plant is a result of impaired autophagy.

Hydrogel-based molecular tension fluorescence microscopy for investigating receptor-mediated rigidity sensing.

Extracellular matrix (ECM) rigidity serves as a crucial mechanical cue impacting diverse biological processes. However, understanding the molecular mechanisms of rigidity sensing has been limited by the spatial resolution and force sensitivity of current cellular force measurement techniques. Here we developed a method to functionalize DNA tension probes on soft hydrogel surfaces in a controllable and reliable manner, enabling molecular tension fluorescence microscopy for rigidity sensing studies. Our findings showed that fibroblasts respond to substrate rigidity by recruiting more force-bearing integrins and modulating integrin sampling frequency of the ECM, rather than simply overloading the existing integrin-ligand bonds, to promote focal adhesion maturation. We also demonstrated that ECM rigidity positively regulates the pN force of T cell receptor-ligand bond and T cell receptor mechanical sampling frequency, promoting T cell activation. Thus, hydrogel-based molecular tension fluorescence microscopy implemented on a standard confocal microscope provides a simple and effective means to explore detailed molecular force information for rigidity-dependent biological processes.

Transcriptional and epigenetic decoding of the microglial aging process.

As important immune cells, microglia undergo a series of alterations during aging that increase the susceptibility to brain dysfunctions. However, the longitudinal characteristics of microglia remain poorly understood. In this study, we mapped the transcriptional and epigenetic profiles of microglia from 3- to 24-month-old mice. We first discovered unexpected sex differences and identified age-dependent microglia (ADEM) genes during the aging process. We then compared the features of aging and reactivity in female microglia at single-cell resolution and epigenetic level. To dissect functions of aged microglia excluding the influence from other aged brain cells, we established an accelerated microglial turnover model without directly affecting other brain cells. By this model, we achieved aged-like microglia in non-aged brains and confirmed that aged-like microglia per se contribute to cognitive decline. Collectively, our work provides a comprehensive resource for decoding the aging process of microglia, shedding light on how microglia maintain brain functions.

Exploring Mechanical Responses of Cells to Geometric Information Using Micropatterned DNA-Based Molecular Tension Probes.

The geometric shape of a cell is strongly influenced by the cytoskeleton, which, in turn, is regulated by integrin-mediated cell-extracellular matrix (ECM) interactions. To investigate the mechanical role of integrin in the geometrical interplay between cells and the ECM, we proposed a single-cell micropatterning technique combined with molecular tension fluorescence microscopy (MTFM), which allows us to characterize the mechanical properties of cells with prescribed geometries. Our results show that the curvature is a key geometric cue for cells to differentiate shapes in a membrane-tension- and actomyosin-dependent manner. Specifically, curvatures affect the size of focal adhesions (FAs) and induce a curvature-dependent density and spatial distribution of strong integrins. In addition, we found that the integrin subunit ß1 plays a critical role in the detection of geometric information. Overall, the integration of MTFM and single-cell micropatterning offers a robust approach for investigating the nexus between mechanical cues and cellular responses, holding potential for advancing our understanding of mechanobiology.

Molecular Force Imaging Reveals That Integrin-Dependent Mechanical Checkpoint Regulates Fcγ-Receptor-Mediated Phagocytosis in Macrophages.

Macrophages are a type of immune cell that helps eliminate pathogens and diseased cells. Recent research has shown that macrophages can sense mechanical cues from potential targets to perform effective phagocytosis, but the mechanisms behind it remain unclear. In this study, we used DNA-based tension probes to study the role of integrin-mediated forces in FcγR-mediated phagocytosis. The results showed that when the phagocytic receptor FcγR is activated, the force-bearing integrins create a "mechanical barrier" that physically excludes the phosphatase CD45 and facilitates phagocytosis. However, if the integrin-mediated forces are physically restricted at lower levels or if the macrophage is on a soft matrix, CD45 exclusion is significantly reduced. Moreover, CD47-SIRPα "don't eat me" signaling can reduce CD45 segregation by inhibiting the mechanical stability of the integrin barrier. These findings demonstrate how macrophages use molecular forces to identify physical properties and combine them with biochemical signals from phagocytic receptors to guide phagocytosis.

Mapping Neurophysiological Subtypes of Major Depressive Disorder Using Normative Models of the Functional Connectome.

BACKGROUND: Major depressive disorder (MDD) is a highly heterogeneous disorder that typically emerges in adolescence and can occur throughout adulthood. Studies aimed at quantitatively uncovering the heterogeneity of individual functional connectome abnormalities in MDD and identifying reproducibly distinct neurophysiological MDD subtypes across the lifespan, which could provide promising insights for precise diagnosis and treatment prediction, are still lacking. METHODS: Leveraging resting-state functional magnetic resonance imaging data from 1148 patients with MDD and 1079 healthy control participants (ages 11-93), we conducted the largest multisite analysis to date for neurophysiological MDD subtyping. First, we characterized typical lifespan trajectories of functional connectivity strength based on the normative model and quantitatively mapped the heterogeneous individual deviations among patients with MDD. Then, we identified neurobiological MDD subtypes using an unsupervised clustering algorithm and evaluated intersite reproducibility. Finally, we validated the subtype differences in baseline clinical variables and longitudinal treatment predictive capacity. RESULTS: Our findings indicated great intersubject heterogeneity in the spatial distribution and severity of functional connectome deviations among patients with MDD, which inspired the identification of 2 reproducible neurophysiological subtypes. Subtype 1 showed severe deviations, with positive deviations in the default mode, limbic, and subcortical areas and negative deviations in the sensorimotor and attention areas. Subtype 2 showed a moderate but converse deviation pattern. More importantly, subtype differences were observed in depressive item scores and the predictive ability of baseline deviations for antidepressant treatment outcomes. CONCLUSIONS: These findings shed light on our understanding of different neurobiological mechanisms underlying the clinical heterogeneity of MDD and are essential for developing personalized treatments for this disorder.

Data-driven evolutionary game models for the spread of fairness and cooperation in heterogeneous networks.

Unique large-scale cooperation and fairness norms are essential to human society, but the emergence of prosocial behaviors is elusive. The fact that heterogeneous social networks prevail raised a hypothesis that heterogeneous networks facilitate fairness and cooperation. However, the hypothesis has not been validated experimentally, and little is known about the evolutionary psychological basis of cooperation and fairness in human networks. Fortunately, research about oxytocin, a neuropeptide, may provide novel ideas for confirming the hypothesis. Recent oxytocin-modulated network game experiments observed that intranasal administration of oxytocin to a few central individuals significantly increases global fairness and cooperation. Here, based on the experimental phenomena and data, we show a joint effect of social preference and network heterogeneity on promoting prosocial behaviors by building evolutionary game models. In the network ultimatum game and the prisoner's dilemma game with punishment, inequality aversion can lead to the spread of costly punishment for selfish and unfair behaviors. This effect is initiated by oxytocin, then amplified via influential nodes, and finally promotes global cooperation and fairness. In contrast, in the network trust game, oxytocin increases trust and altruism, but these effects are confined locally. These results uncover general oxytocin-initiated mechanisms underpinning fairness and cooperation in human networks.

Robot-Assisted Bimanual Training Improves Hand Function in Patients With Subacute Stroke: A Randomized Controlled Pilot Study.

Study Design: A randomized controlled pilot study. Background: Bimanual therapy (BMT) is an effective neurorehabilitation therapy for the upper limb, but its application to the distal upper limb is limited due to methodological difficulties. Therefore, we applied an exoskeleton hand to perform robot-assisted task-oriented bimanual training (RBMT) in patients with stroke. Objective: To characterize the effectiveness of RBMT in patients with hemiplegic stroke with upper limb motor impairment. Interventions: A total of 19 patients with subacute stroke (1-6 months from onset) were randomized and allocated to RBMT and conventional therapy (CT) groups. The RBMT and CT groups received 90 min of training/day (RBMT: 60 min RBMT + 30 min CT; CT: 60 min CT for hand functional training + 30 min regular CT), 5 days/week, for 4 weeks (20 sessions during the experimental period). Assessments: Clinical assessments, including the Fugl-Meyer assessment of the upper extremity (FMA-UE), action research arm test (ARAT), and wolf motor arm function test (WMFT), were conducted before and after the intervention. Results: Within-group analysis showed a significant improvement in the FMA-UE and WMFT in both the CT and RBMT groups. A significant improvement in the Fugl-Meyer assessment (FMA) of the wrist and hand for the distal part in the RBMT group occurred earlier than that in the CT group. A significant improvement in WMFT time was found in both groups, but the WMFT functional ability assessment was only found in the RBMT group. No significant improvements in ARAT assessment were observed in either the CT or RBMT groups. Compared with CT, significant improvements were found in terms of the proportion of minimally clinically important differences after RBMT in FMA-UE (χ2 = 4.34, p = 0.037). No adverse events were reported by any of the participants across all sessions. Conclusions: This study is the first to apply RBMT to the distal part of the upper limb. Both RBMT and CT are effective in improving the upper limb function in patients with subacute stroke. RBMT shows superior potential efficacy in facilitating recovery of the distal part of upper extremity (UE) motor function in the early stage. Future randomized control studies with a large sample size and follow-up assessments are needed to validate the present conclusions.