Test–Retest Reliability of Mismatch Negativity (MMN) to Emotional Voices

A voice from kin species conveys indispensable social and affective signals with uniquely phylogenetic and ontogenetic standpoints. However, the neural underpinning of emotional voices, beyond low-level acoustic features, activates a processing chain that proceeds from the auditory pathway to the brain structures implicated in cognition and emotion. By using a passive auditory oddball paradigm, which employs emotional voices, this study investigates the test–retest reliability of emotional mismatch negativity (MMN), indicating that the deviants of positively (happily)- and negatively (angrily)-spoken syllables, as compared to neutral standards, can trigger MMN as a response to an automatic discrimination of emotional salience. The neurophysiological estimates of MMN to positive and negative deviants appear to be highly reproducible, irrespective of the subject’s attentional disposition: whether the subjects are set to a condition that involves watching a silent movie or do a working memory task. Specifically, negativity bias is evinced as threatening, relative to positive vocalizations, consistently inducing larger MMN amplitudes, regardless of the day and the time of a day. The present findings provide evidence to support the fact that emotional MMN offers a stable platform to detect subtle changes in current emotional shifts

The Developmental Origins of the Social Brain: Empathy, Morality, and Justice

The social brain is the cornerstone that effectively negotiates and navigates complex social environments and relationships. When mature, these social abilities facilitate the interaction and cooperation with others. Empathy, morality, and justice, among others, are all closely intertwined, yet the relationships between them are quite complex. They are fundamental components of our human nature, and shape the landscape of our social lives. The various facets of empathy, including affective arousal/emotional sharing, empathic concern, and perspective taking, have unique contributions as subcomponents of morality. This review helps understand how basic forms of empathy, morality, and justice are substantialized in early ontogeny. It provides valuable information as to gain new insights into the underlying neurobiological precursors of the social brain, enabling future translation toward therapeutic and medical interventions

Atypical Anxiety-Related Amygdala Reactivity and Functional Connectivity in Sant Mat Meditation

While meditation has drawn much attention in cognitive neuroscience, the neural mechanisms underlying its emotional processing remains elusive. Sant Mat meditators were recruited, who adopt a loving-kindness mode of meditation along with a vegetarian diet and an alcohol-restricted lifestyle and novices. We assessed their State-Trait Anxiety Inventory (STAI) and scanned their amygdala reactivity in response to an explicit and implicit (backward masked) perception of fearful and happy faces. In contrast with novices, meditators reported lower STAI scores. Meditators showed stronger amygdala reactivity to explicit happiness than to fear, whereas novices exhibited the opposite pattern. The amygdala reactivity was reduced in meditators regardless of implicit fear or happiness. Those who had more lifetime practice in meditation reported lower STAI and showed a weaker amygdala response to fear. Furthermore, the amygdala in meditators, relative to novices, had a stronger positive functional connectivity with the ventrolateral prefrontal cortex (PFC) to explicit happiness, but a more negative connectivity with the insula and medial orbitofrontal cortex (OFC) to explicit fear. Mediation analysis indicated the amygdala reactivity as the mediator for the linkage between meditation experience and trait anxiety. The findings demonstrate the neural correlates that underpin the beneficial effects of meditation in Sant Mat. Long-term meditation could be functionally coupled with the amygdala reactivity to explicit and implicit emotional processing, which would help reduce anxiety and potentially enhance well-being

Progress in genetic mechanisms and precise treatment of neurocutaneous syndrome-related epilepsy

Neurocutaneous syndromes are a group of genetic disorders involving the nervous and cutaneous systems, including Tuberous Sclerosis Complex (TSC), neurofibromatosis type 1 (NF1), and Sturge–Weber syndrome (SWS), and others. The incidence of epilepsy, a core clinical manifestation, is significantly higher than in the general population. The purpose of this narrative review is to provide an updated overview of the genetic mechanisms and recent advances in precise treatment for neurocutaneous syndrome-related epilepsy. We conducted a comprehensive search of the PubMed, Scopus, EMBASE, and Web of Science databases using all MeSH terms related to ‘Neurocutaneous Syndromes’, ‘Epilepsy/genetics’, ‘Signal Transduction’, and ‘Precision Medicine’. Selected papers underwent review and risk of bias (RoB) assessment to evaluate core questions. Somatic or germline mutations dysregulate key signaling pathways (e.g., mTOR, Ras-MAPK, PI3K-AKT), inducing malformations of cortical development (MCD) and neuronal-glial dysfunction that collectively form epileptogenic networks. This constitutes the primary pathogenic mechanism underlying neurocutaneous syndrome-related epilepsy. Precise treatment strategies based on molecular mechanisms have achieved breakthroughs: mTOR inhibitors significantly reduce seizure frequency in TSC patients, and cannabidiol (CBD) demonstrates broad-spectrum antiepileptic efficacy in TSC and Dravet syndrome. Advances in surgical techniques, such as multimodal imaging-guided resection, improve outcomes in refractory epilepsy. However, clinical translation faces challenges including technical limitations in detecting mosaic mutations, insufficient specificity of targeted drugs, and interdisciplinary collaboration gaps. Future directions require integrating multi-omics technologies, developing novel gene therapies (e.g., CRISPR-based approaches), and establishing multicenter databases linking genotype–phenotype-treatment responses to advance personalized precision medicine

SOAR elucidates biological insights and empowers drug discovery through spatial transcriptomics

Spatial transcriptomics enables multiplex profiling of gene cellular expression and location within the tissue context. Although large volumes of spatial transcriptomics data have been generated, the lack of systematic curation and analysis limits biological discovery. We present Spatial transcriptOmics Analysis Resource (SOAR), a comprehensive spatial transcriptomics platform with 3461 uniformly processed samples across 13 species, 42 tissue types, and 19 different spatial transcriptomics technologies. Using SOAR, we found that CXCL16/SPP1 macrophage polarity characterizes the coordination of immune cell polarity in the tumor microenvironment. SOAR’s integrative approach toward drug discovery revealed sirolimus and trichostatin A as potential anticancer agents targeting the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin growth and proliferation pathway and identified Janus kinase/signal transducers and activators of transcription inhibitors for ulcerative colitis treatment. SOAR’s results demonstrate its broad application to data generated from diverse spatial technologies and pathological conditions. SOAR will support future benchmarking studies and method development, facilitating discoveries in molecular functions, disease mechanisms, and potential therapeutic targets

Effects of chronic intermittent hypobaric hypoxia on expression and promoter region methylation of key enzyme genes related to glucose metabolism in diabetic mice

BackgroundChronic intermittent hypobaric hypoxia (CIHH) can effectively alleviate type 2 diabetes mellitus (T2DM). In this process, the underlying mechanism in its association with the epigenetic regulation of DNA methylation in the promoter regions of glucose metabolism key enzyme genes remains unclear yet.ObjectiveTo investigate the effects of CIHH on expression and promoter region methylation of key enzyme genes related to glucose metabolism in diabetes mice, and to explore the underlying mechanism by which CIHH regulates glucose metabolism.MethodsForty C57BL/6J male mice were divided randomly into a normobaric normoxic control (NN/CON) group, a chronic intermittent hypobaric hypoxia intervention control (CIHH/CON) group, a normobaric normoxic diabetic model (NN/DM) group, and a chronic intermittent hypobaric hypoxia intervention diabetic model (CIHH/DM) group. The mice in the NN/DM and the CIHH/DM groups were fed for 7 weeks with high-fat and high-sugar diet. Subsequently, these mice were intraperitoneally injected consecutively with 50 mmol·L−1 streptozotocin (STZ) for 5 d at a dose of 40 mg·kg−1 (body weight) per day to create T2DM model mice. The mice in the CIHH/DM and the CIHH/CON groups were intervened by simulating hypobaric hypoxia at 5000 m altitude for 6 h per day, while the mice in the NN/DM and the NN/CON groups were always placed in a normobaric normoxic environment. All mice were continuously treated for 4 weeks, and blood glucose were monitored during this period. After the CIHH intervention experiment, the glucose tolerance and insulin sensitivity of mice were evaluated. A set of indicators involved in key glycolytic enzymes glucokinase (GK) and pyruvate kinase (PK), as well as key gluconeogenic enzymes phosphoenolpyruvate carboxyl kinase (PEPCK) and glucose-6-phosphatase (G6P) were measured in the liver of mice, including enzyme activity, relative mRNA expression level, and DNA methylation level in the gene promoter regions.ResultsCompared with the mice in the NN/DM group, the blood glucose levels of the mice in the CIHH/DM group decreased after the 25th day of the CIHH intervention (P0.05), and their correlations with mRNA expression levels were also not statistically significant (P>0.05).ConclusionCIHH intervention may reduce blood glucose level, improve glucose tolerance, alleviate insulin resistance, and regulate the key enzyme activities of glucose metabolism and the relative mRNA expression of their corresponding genes in T2DM mice, but the above phenomena are not related to the DNA methylation levels in the promoter regions of these key enzymes

Sub-millisecond pulsed laser engineering of CuOx-decorated Pd nanoparticles for enhanced catalytic CO2 hydrogenation

Catalytic CO2 hydrogenation to fuels and chemicals presents a promising avenue for addressing global warming and advancing toward a net-zero economy. Surface atomic rearrangement of catalysts has attracted growing interest as a means to manipulate catalyst activity and selectivity. Herein, we designed a ternary nanocatalyst comprising CuOx species decorated Pd nanoparticles (NPs) supported on Co oxide (denoted as CPCu) for catalytic CO2 hydrogenation. Sub-millisecond laser treatment (1 mJ per pulse) was used to manipulate the surface atomic arrangements of CPCu the catalyst. The CPCu nanocatalyst showed a significant enhancement in both CH4 production and CO production at 300 °C compared to the Pd/Co catalyst. Notably, the CH4 production using the laser-treated nanocatalyst (denoted as CPCu-L) was 66.6 % higher than the untreated one (CPCu) at 300 °C. Comprehensive catalyst characterizations revealed that CuOx species promoted CO2 activation, while neighboring Pd domains effectively dissociated H2 molecules, leading to enhanced CH4 production. This study demonstrates the potential of sub-millisecond laser treatment for tailoring catalyst surfaces, offering a promising strategy to design more active and selective catalysts for CO2 hydrogenation

Exploring the differential functions of circulating follicular helper T and peripheral helper T cells in rheumatoid arthritis based on metabolism patterns

IntroductionThe number of circulating follicular helper T (cTfh) and peripheral helper T (Tph) cells is elevated in rheumatoid arthritis (RA), yet the molecular mechanisms mediating their specific contributions to RA pathology remain unclear. In this study, we explored the distinct function of cTfh and Tph cells based on metabolism patterns in RA.MethodsPeripheral CD4+ T cells from RA patients were treated with CXCL13 or CCL2, glycolysis inhibitor 2-DG or mitochondria-targeted antioxidant MitoQ in vitro. Collagen induced arthritis (CIA) mice were treated with 2-DG or MitoQ in vivo. The frequency, transcription factors, functional molecules, cellular senescence, glycolytic activity and mitochondrial ROS (mtROS) of cTfh and Tph cells were assessed. Joint inflammation, CD4+PD-1+ T cells, glycolytic enzymes or IL-1β and IL-6 in ankle joints of CIA mice were detected.ResultsWe found that in RA patients, in comparison with Tph cells, cTfh cells show higher levels of Bcl6 and BATF, B helper-related molecules, and glycolytic activity. While Tph cells exhibit higher levels of Blimp1 and T-bet, cytotoxicity-related molecules and mtROS, and more significant cellular senescence characteristics. In addition, CXCL13, the ligand for CXCR5, increases the expression of key glycolytic enzymes in RA cTfh cells, while CCL2 increases mtROS in RA Tph cells. 2-DG reduces the expression of B helper-related molecules cells, and MitoQ mitigates cytotoxic activity of cTfh and Tph cells. Both treatments ameliorate RA symptoms and decrease the number of cTfh and Tph cells in CIA mice.ConclusionOur study suggests that in RA patients, cTfh cells display a more robust B helper-associated function, potentially linked to the CXCL13-CXCR5 axis enhancing glycolysis. Tph cells, on the other hand, show greater cytotoxic activity, possibly due to the CCL2-CCR2 axis increasing mtROS production. Targeting glycolysis or mtROS may offer a novel therapeutic strategy for RA patients