Temporal neural dynamics of understanding communicative intentions from speech prosody.

Understanding the correct intention of a speaker is critical for social interaction. Speech prosody is an important source for understanding speakers' intentions during verbal communication. However, the neural dynamics by which the human brain translates the prosodic cues into a mental representation of communicative intentions in real time remains unclear. Here, we recorded EEG (electroencephalograph) while participants listened to dialogues. The prosodic features of the critical words at the end of sentences were manipulated to signal either suggestion, warning, or neutral intentions. The results showed that suggestion and warning intentions evoked enhanced late positive event-related potentials (ERPs) compared to the neutral condition. Linear mixed-effects model (LMEM) regression and representational similarity analysis (RSA) analyses revealed that these ERP effects were distinctively correlated with prosodic acoustic analysis, emotional valence evaluation, and intention interpretation in different time windows; The onset latency significantly increased as the processing level of abstractness and communicative intentionality increased. Neural representations of intention and emotional information emerged and parallelly persisted over a long time window, guiding the correct identification of communicative intention. These results provide new insights into understanding the structural components of intention processing and their temporal neural dynamics underlying communicative intention comprehension from speech prosody in online social interactions.

Baicalein ameliorates chronic itch in ACD mice by suppressing the spinal astrocytic STAT3-LCN2 cascade.

Chronic itch is a maladaptive and debilitating symptom in patients with allergic contact dermatitis (ACD), adversely affecting their quality of life. There is a lack of effective treatments for ACD-associated uncontrollable itch. In this study, we explored the antipruritic effects of baicalein (BE), a bioactive flavonoid extracted from the root of Scutellaria baicalensis Georgi, and the underlying mechanisms in alleviating chronic itch triggered by diphenylcyclopropenone (DCP) in a mouse model of ACD. The ACD mice were intraperitoneally injected with BE (5, 30, and 60 mg·kg-1·d-1) for 7 days during the DCP challenge phase. The results showed that DCP-treated mice exhibited severe spontaneous scratching behaviors that was reduced after BE injections in a dose-dependent manner accompanied by inhibition of spinal astrocyte activation. We observed that the spinal astrocytic STAT3-LCN2 cascade plays a crucial role in controlling the activation of astrocytes in chronic itch. Intrathecal injection of the STAT3 inhibitor AG490 or Lcn2 siRNA significantly reduced scratching behavior and astrocyte activation in ACD mice. Moreover, BE markedly attenuated the increased phosphorylation of STAT3 (p-STAT3) and LCN2 expression in the spinal cords of ACD mice and in lipopolysaccharide-stimulated primary spinal astrocytes. Altogether, BE relieved chronic itch by suppressing the spinal astrocytic STAT3-LCN2 cascade. These findings provide a potential avenue for the management of chronic itch. Schematic summary of the main findings illustrating that BE alleviates chronic itch through suppressing the spinal astrocytic STAT3-LCN2 cascade. Specifically, BE suppresses the expression of p-STAT3 to inhibit the reactive state of astrocytes in spinal dorsal horn, and then decreases the expression of astrocytic LCN2 to alleviate chronic itch in ACD mice.

Effective treatment of traumatic brain injury by injection of a selenium-containing ointment.

Traumatic brain injury (TBI) is an incurable and overwhelming disease accompanied with serve disability and huge financial burden, where the overproduced reactive oxygen species (ROS) can exacerbate the secondary injury, leading to massive apoptosis of neurons. In this study, ß-cyclodextrin (CD)-capped hyperbranched polymers containing selenium element (HSE-CD) were crosslinked with CD-modified hyaluronic acid (HA-CD) and amantadine-modified hyaluronic acid (HA-AD) to obtain a ROS-responsive ointment (R-O). The structures of synthesized polymers were characterized with 1H nuclear magnetic resonance, and the properties of ointment were investigated with rheology and antioxidation. Compared to non-ROS-responsive ointment (N-O), the R-O ointment had stronger efficiency in decreasing the ROS level in BV2 cells in vitro. In a controlled rat cortical impact (CCI) model, the R-O ointment could relieve the DNA damage and decrease apoptosis in injured area via reducing the ROS level. Besides, after the R-O treatment, the rats showed significantly less activated astrocytes and microglia, a lower level of pro-inflammatory cytokines and a higher ratio of M2/M1 macrophage and microglia. Moreover, compared to the TBI group the R-O ointment promoted the doublecortin (DCX) expression and tissue structure integrity around the cavity, and promoted the recovery of nerve function post TBI. STATEMENT OF SIGNIFICANCE: Traumatic brain injury (TBI) is an incurable and overwhelming disease, leading to severe disability and huge social burden, where reactive oxygen species (ROS) are considered as one of the most significant factors in the secondary injury of TBI. A ROS responsive supramolecular ointment containing di-selenide bonds was injected in rats with controlled cortical impact. It relieved the DNA damage and decreased apoptosis in the injured area via reducing the ROS levels, downregulated neuroinflammation, and improved neurological recovery of TBI in vivo. This designed self-adaptive biomaterial effectively regulated the pathological microenvironment in injured tissue, and achieved better therapeutic effect.

Musical tension is affected by metrical structure dynamically and hierarchically.

As the basis of musical emotions, dynamic tension experience is felt by listeners as music unfolds over time. The effects of musical harmonic and melodic structures on tension have been widely investigated, however, the potential roles of metrical structures in tension perception remain largely unexplored. This experiment examined how different metrical structures affect tension experience and explored the underlying neural activities. The electroencephalogram (EEG) was recorded and subjective tension was rated simultaneously while participants listened to music meter sequences. On large time scale of whole meter sequences, it was found that different overall tension and low-frequency (1 ~ 4 Hz) steady-state evoked potentials were elicited by metrical structures with different periods of strong beats, and the higher overall tension was associated with metrical structure with the shorter intervals between strong beats. On small time scale of measures, dynamic tension fluctuations within measures was found to be associated with the periodic modulations of high-frequency (10 ~ 25 Hz) neural activities. The comparisons between the same beats within measures and across different meters both on small and large time scales verified the contextual effects of meter on tension induced by beats. Our findings suggest that the overall tension is determined by temporal intervals between strong beats, and the dynamic tension experience may arise from cognitive processing of hierarchical temporal expectation and attention, which are discussed under the theoretical frameworks of metrical hierarchy, musical expectation and dynamic attention.

Biofluorescence imaging-guided spatial metabolic tracing: In vivo tracking of metabolic activity in circulating tumor cell-mediated multi-organ metastases.

Circulating tumor cells (CTC) are considered metastatic precursors that are shed from the primary or metastatic deposits and navigate the bloodstream before undergoing extravasation to establish distant metastases. Metabolic reprogramming appears to be a hallmark of metastatic progression, yet current methods for evaluating metabolic heterogeneity within organ-specific metastases in vivo are limited. To overcome this challenge, we present Biofluorescence Imaging-Guided Spatial Metabolic Tracing (BIGSMT), a novel approach integrating in vivo biofluorescence imaging, stable isotope tracing, stain-free laser capture microdissection, and liquid chromatography-mass spectrometry. This innovative technology obviates the need for staining or intricate sample preparation, mitigating metabolite loss, and substantially enhances detection sensitivity and accuracy through chemical derivatization of polar metabolites in central carbon pathways. Application of BIGSMT to a preclinical CTC-mediated metastasis mouse model revealed significant heterogeneity in the in vivo carbon flux from glucose into glycolysis and the tricarboxylic acid (TCA) cycle across distinct metastatic sites. Our analysis indicates that carbon predominantly enters the TCA cycle through the enzymatic reaction catalyzed by pyruvate dehydrogenase. Thus, our spatially resolved BIGSMT technology provides fresh insights into the metabolic heterogeneity and evolution during melanoma CTC-mediated metastatic progression and points to novel therapeutic opportunities.

Ball-Milling-Enabled Nickel-Catalyzed Reductive 1,4-Alkylarylation of 1,3-Enynes under an Air Atmosphere.

A ball-mill-enabled nickel-catalyzed 1,4-alkylarylation of 1,3-enynes with organic bromides has been developed, offering a versatile method for assembling tetrasubstituted allenes. This approach, the first of ball-milling-based remote radical coupling, overcomes the limitations of traditional solution-phase methods, such as the need for air- and moisture-sensitive reagents, the use of bulk solvents, and prolonged reaction times. Given the outstanding performance of ball-milling-based radical reduction coupling reactions, we anticipate further advancements in sustainable and efficient synthetic methodologies.

Pathogenic genes implicated in sleep-related hypermotor epilepsy: a research progress update.

Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy syndrome characterized by a variable age of onset and heterogeneous etiology. Current literature suggests a prevalence rate of approximately 1.8 per 100,000 persons. The discovery of additional pathogenic genes associated with SHE in recent years has significantly expanded the knowledge and understanding of its pathophysiological mechanisms. Identified SHE pathogenic genes include those related to neuronal ligand- and ion-gated channels (CHRNA4, CHRNB2, CHRNA2, GABRG2, and KCNT1), genes upstream of the mammalian target of rapamycin complex 1 signal transduction pathway (DEPDC5, NPRL2, NPRL3, TSC1, and TSC2), and other genes (CRH, CaBP4, STX1B, and PRIMA1). These genes encode proteins associated with ion channels, neurotransmitter receptors, cell signal transduction, and synaptic transmission. Mutations in these genes can result in the dysregulation of encoded cellular functional proteins and downstream neuronal dysfunction, ultimately leading to epileptic seizures. However, the associations between most genes and the SHE phenotype remain unclear. This article presents a literature review on the research progress of SHE-related pathogenic genes to contribute evidence to genotype-phenotype correlations in SHE and establish the necessary theoretical basis for future SHE treatments.

Generation of true quantum random numbers with on-demand probability distributions via single-photon quantum walks.

Random numbers are at the heart of diverse fields, ranging from simulations of stochastic processes to classical and quantum cryptography. The requirement for true randomness in these applications has motivated various proposals for generating random numbers based on the inherent randomness of quantum systems. The generation of true random numbers with arbitrarily defined probability distributions is highly desirable for applications, but it is very challenging. Here we show that single-photon quantum walks can generate multi-bit random numbers with on-demand probability distributions, when the required "coin" parameters are found with the gradient descent (GD) algorithm. Our theoretical and experimental results exhibit high fidelity for various selected distributions. This GD-enhanced single-photon system provides a convenient way for building flexible and reliable quantum random number generators. Multi-bit random numbers are a necessary resource for high-dimensional quantum key distribution.

Research progress on the fanconi anemia signaling pathway in non-obstructive azoospermia.

Non-obstructive azoospermia (NOA) is a disease characterized by spermatogenesis failure and comprises phenotypes such as hypospermatogenesis, mature arrest, and Sertoli cell-only syndrome. Studies have shown that FA cross-linked anemia (FA) pathway is closely related to the occurrence of NOA. There are FA gene mutations in male NOA patients, which cause significant damage to male germ cells. The FA pathway is activated in the presence of DNA interstrand cross-links; the key step in activating this pathway is the mono-ubiquitination of the FANCD2-FANCI complex, and the activation of the FA pathway can repair DNA damage such as DNA double-strand breaks. Therefore, we believe that the FA pathway affects germ cells during DNA damage repair, resulting in minimal or even disappearance of mature sperm in males. This review summarizes the regulatory mechanisms of FA-related genes in male azoospermia, with the aim of providing a theoretical reference for clinical research and exploration of related genes.

The spontaneous activities of the multiple demand network are related to individual differences in indirect replies comprehension.

This study aims to investigate the brain networks engaged in the comprehension of indirect language, as well as the individual difference in this capacity. Specially, we aim to determine whether the difference is solely influenced by the difference in individuals' default network (DN)/language network or whether it also relies on the networks associated with processing of complex cognitive tasks, particularly the multiple demand network (MDN). Conversational indirectness scale (CIS) scores in the interpretation dimension were used as a behavioral indicator of the indirect comprehension tendency. Reading time difference between indirect replies and direct replies collected through a self-paced reading experiment was deemed as a behavioral indicator of comprehension speed of indirect replies comprehension. The two behavioral indicators were combined with resting-state functional magnetic resonance imaging (rs-fMRI). The behaviour-rfMRI analysis showed that ALFF value of right SPL and the functional connectivity (FC) between the right SPL and right IPL/SMA/ITG/Precuneus/bilateral IFG were positively correlated with the interpretation dimension of CIS scores. In addition, the ALFF value of right fusiform gyrus, the FC between the right fusiform gyrus and right precuneus, and the FCs between right SPL and right IPL/Precuneus/IFG were negatively correlated with indirect replies comprehension speed. Overlapping of these regions with large-scale brain network revealed that the right SPL was mainly located in the MDN, and the right fusiform gyrus was mainly located in the language network. Additionally, the areas showing functional connectivity with these regions were primarily located in the MDN, with a smaller subset located in the DN. Our findings suggest that the ability of individuals to actively and rapidly acquire indirect meaning relies not only on the support of the DN and the language network, but also requires collective support from the MDN.

ChineseEEG: A Chinese Linguistic Corpora EEG Dataset for Semantic Alignment and Neural Decoding.

An Electroencephalography (EEG) dataset utilizing rich text stimuli can advance the understanding of how the brain encodes semantic information and contribute to semantic decoding in brain-computer interface (BCI). Addressing the scarcity of EEG datasets featuring Chinese linguistic stimuli, we present the ChineseEEG dataset, a high-density EEG dataset complemented by simultaneous eye-tracking recordings. This dataset was compiled while 10 participants silently read approximately 13 hours of Chinese text from two well-known novels. This dataset provides long-duration EEG recordings, along with pre-processed EEG sensor-level data and semantic embeddings of reading materials extracted by a pre-trained natural language processing (NLP) model. As a pilot EEG dataset derived from natural Chinese linguistic stimuli, ChineseEEG can significantly support research across neuroscience, NLP, and linguistics. It establishes a benchmark dataset for Chinese semantic decoding, aids in the development of BCIs, and facilitates the exploration of alignment between large language models and human cognitive processes. It can also aid research into the brain's mechanisms of language processing within the context of the Chinese natural language.

Electroacupuncture ameliorates neuroinflammation by inhibiting TRPV4 channel in ischemic stroke.

AIMS: We investigated the potential mechanisms underlying the therapeutic efficacy of electroacupuncture (EA) at the Shuigou (GV26) and Baihui (GV20) acupoints in the treatment of ischemic stroke. METHODS: We assessed the therapeutic effects of EA on MCAO mice through behavioral studies and TTC staining. Various techniques, such as RT-PCR, immunofluorescence, and Western blots, were employed to evaluate the activation and polarization of microglia/macrophages, and changes in the TRPV4 ion channel. We used the TRPV4 antagonist GSK2193874 (GSK219) to verify the involvement of TRPV4 in the therapeutic effects of EA. RESULTS: EA effectively improved neurological impairments and reduced cerebral infarction volume in MCAO mice. It suppressed activated microglia/macrophages and inhibited their polarization toward the M1 phenotype post-MCAO. EA also downregulated the expression of pro-inflammatory cytokines, including Tnf-α, Il-6, Il-1ß, and Ccl-2 mRNA. Furthermore, EA reduced the elevated expression of TRPV4 following MCAO. Treatment with the TRPV4 antagonist GSK219 mirrored the effects of EA in MCAO mice. Notably, the combination of EA and GSK219 did not demonstrate an additive or synergistic effect. CONCLUSION: EA may inhibit neuroinflammation and exhibit a protective effect against ischemic brain injury by suppressing TRPV4 and the subsequent M1 polarization of microglia/macrophages.

Herb pair of Rhubarb-Astragalus mitigates renal interstitial fibrosis through downregulation of autophagy via p38-MAPK/TGF-ß1 and p38-MAPK/smad2/3 pathways.

BACKGROUND: Chronic kidney disease (CKD) has a high incidence and poor prognosis; however, no effective treatment is currently available. Our previous study found that the improvement effect of the herb pair of Rhubarb-Astragalus on CKD is likely related to the inhibition of the TGF-ß1/p38-MAPK pathway. In the present study, a p38-MAPK inhibitor was used to further investigate the inhibitory effect of Rhubarb-Astragalus on the TGF-ß1/p38-MAPK pathway and its relationship with autophagy. METHODS: A rat model of unilateral ureteral obstruction (UUO) was established, and a subgroup of rats was administered Rhubarb-Astragalus. Renal function and renal interstitial fibrosis (RIF) were assessed 21 d after UUO induction. In vitro, HK-2 cells were treated with TGF-ß1 and a subset of cells were treated with Rhubarb-Astragalus or p38-MAPK inhibitor. Western blotting, immunohistochemistry, and qRT-PCR analyses were used to detect the relevant protein and mRNA levels. Transmission electron microscopy was used to observe autophagosomes. RESULTS: Rhubarb-Astragalus treatment markedly decreased the elevated levels of blood urea nitrogen, serum creatinine, and urinary N-acetyl-ß-D-glucosaminidase; attenuated renal damage and RIF induced by UUO; and reduced the number of autophagosomes and lysosomes in UUO-induced renal tissues. Additionally, Rhubarb-Astragalus reduced the protein and mRNA levels of α-SMA, collagen I, LC3, Atg3, TGF-ß1, p38-MAPK, smad2/3, and TAK1 in renal tissues of UUO rats. Rhubarb-Astragalus also reduced protein and mRNA levels of these indicators in vitro. Importantly, the effect of the p38-MAPK inhibitor was similar to that of Rhubarb-Astragalus. CONCLUSIONS: Rhubarb-Astragalus improves CKD possibly by downregulating autophagy via the p38-MAPK/TGF-ß1 and p38-MAPK/smad2/3 pathways.

Preexposure to one social threat alters responses to another social threat: Behavioral and electrophysiological evidence.

A recent Cyberball study has indicated that the experience of loss of control can affect how people process subsequent social exclusion. This "preexposure effect" supports the idea of a common cognitive system involved in the processing of different types of social threats. To test the validity of this assumption in the current study, we reversed the sequence of the preexposure setup. We measured the effects of social exclusion on the subsequent processing of loss of control utilizing event-related brain potentials (ERPs) and self-reports. In the control group (CG, n = 26), the transition to loss of control elicited significant increases in both the P3 amplitude and the self-reported negative mood. Replicating the results of the previous preexposure study, these effects were significantly reduced by the preexposure to an independent social threat (here: social exclusion). In contrast to previous findings, these effects were not modulated by the discontinuation (EG1disc, n = 25) or continuation (EG2cont, n = 24) of the preexposure threat. Given that the P3 effect is related to the violation of subjective expectations, these results support the notion that preexposure to a specific social threat has widespread effects on the individuals' expectancy of upcoming social participation and control.

EEGManyPipelines: A Large-scale, Grassroots Multi-analyst Study of Electroencephalography Analysis Practices in the Wild.

The ongoing reproducibility crisis in psychology and cognitive neuroscience has sparked increasing calls to re-evaluate and reshape scientific culture and practices. Heeding those calls, we have recently launched the EEGManyPipelines project as a means to assess the robustness of EEG research in naturalistic conditions and experiment with an alternative model of conducting scientific research. One hundred sixty-eight analyst teams, encompassing 396 individual researchers from 37 countries, independently analyzed the same unpublished, representative EEG data set to test the same set of predefined hypotheses and then provided their analysis pipelines and reported outcomes. Here, we lay out how large-scale scientific projects can be set up in a grassroots, community-driven manner without a central organizing laboratory. We explain our recruitment strategy, our guidance for analysts, the eventual outputs of this project, and how it might have a lasting impact on the field.

Does decreased autophagy and dysregulation of LC3A in astrocytes play a role in major depressive disorder?

Astrocytic dysfunction contributes to the molecular pathogenesis of major depressive disorder (MDD). However, the astrocytic subtype that mainly contributes to MDD etiology and whether dysregulated autophagy in astrocytes is associated with MDD remain unknown. Using a single-nucleus RNA sequencing (snRNA-seq) atlas, three astrocyte subtypes were identified in MDD, while C2 State-1Q astrocytes showed aberrant changes in both cell proportion and most differentially expressed genes compared with other subtypes. Moreover, autophagy pathways were commonly inhibited in astrocytes in the prefrontal cortices (PFCs) of patients with MDD, especially in C2 State-1Q astrocytes. Furthermore, by integrating snRNA-seq and bulk transcriptomic data, we found significant reductions in LC3A expression levels in the PFC region of CUMS-induced depressed mice, as well as in postmortem PFC tissues and peripheral blood samples from patients with MDD. These results were further validated by qPCR using whole-blood samples from patients with MDD and healthy controls. Finally, LC3A expression in the whole blood of patients with MDD was negatively associated with the severity of depressive symptoms. Overall, our results underscore autophagy inhibition in PFC astrocytes as a common molecular characteristic in MDD and might reveal a novel potential diagnostic marker LC3A.

Electrophysiological evidence for sensitization effects elicited by concurrent social threats.

Experiencing a social threat, such as social exclusion, is a painful event. In contrast to previous studies providing insight into the processing of a single short-termed threat, we exposed healthy individuals to the simultaneous onset of different social threats. This approach allowed us to track whether these threats are processed independently-or whether they interact in a common system. Using a virtual ball-throwing game (Cyberball), electrophysiological (event-related brain potentials, ERPs) and behavioral (self-reports) responses were collected. We assigned undergraduates to three experimental groups: single threat exclusion (n = 24), single threat loss of control (n = 26), and joint onset of both threats (dual-threat, n = 25). Self-reports indicated an increase in threats (i.e., in perceived exclusion and loss-of-control) in the latter group. The ERPs disentangled the neural responses to each threat: In the dual-threat group, the amplitudes of the P3 responses to exclusionary and intervention events were enhanced. This indicates that individuals are sensitized to each of the threats when the other threat is present simultaneously. Our findings support the theoretical notion of a common cognitive system responding to violations in subjective expectations.

A fish image segmentation methodology in aquaculture environment based on multi-feature fusion model.

Underwater fish image processing is one of the key technologies to realize intelligent aquaculture. However, due to the complexity of marine environments, underwater fish images usually have the characteristics of color cast, unbalanced contrast, and blur. Current underwater fish image segmentation methods lack adaptive models and have low segmentation accuracy. Hence, this paper constructs a convolutional neural network-based image segmentation model. This paper first proposes a fish image preprocessing method based on pixel threshold segmentation. To enhance the important features in a fish image, this method uses the minimum Euclidean distance between the original image peaks to redefine the threshold and fuses the thresholded image with the original image. Second, to strengthen the extraction of high-level semantic features of images, the multiscale attentional feature extraction module (MAFEM), which fuses the adaptive channel attention mechanism with the hybrid dilated convolutional pyramid pooling module, is proposed. In this paper, a data set in voc format is produced based on underwater fish images, and this data set is used to verify the model in this paper. The mean intersection over union (MIoU) reaches 92.6%. Compared with other traditional segmentation models, the MIoU, mean pixel accuracy (MPA), and balanced F score (F1-score) of the segmentation results of the model in this paper are increased by averages of 1.84%, 0.785%, and 1.18%, respectively. The experimental results show that this model has a better segmentation effect than other models and provides a theoretical basis for intelligent monitoring of underwater fish body length measurement, weight estimation, and discrimination of growth and health statuses.

Individual Differences in Emotion Attenuation Brought by Indirect Replies Is Related to Resting-State Brain Activity.

During daily conversations, people prefer indirect replies in face-threatening situations. Existent studies have indicated that recipients tend to perceive the information conveyed by indirect replies as negative and emotion regions are engaged in indirect replies processing in face-threatening situations. In this study, we examined whether indirect replies can reduce recipients' experience of negative emotion and what are the underlying cerebral structures that may give rise to individual differences in the effectiveness of such replies in attenuating negative emotion. Behavior ratings and resting-stating functional magnetic resonance imaging (rs-fMRI) techniques were combined to explore these questions. We created dialogues expressing refusal or negative opinion with direct/indirect replies. Participants were asked to rate their emotional valence and arousal when they received such replies. The rating scores were used to correlate with spontaneous brain activity. Results showed that indirect replies indeed attenuated recipients' negative emotion experience. Moreover, the left caudate, the right anterior cingulate cortex (rACC), and the connectivity of rACC and left medial prefrontal cortex (lmPFC) were found to be positively correlated to individual differences in such emotion attenuation. Our findings provide direct empirical evidence for the face-saving function of indirect replies and reveal that the intrinsic brain activities of emotion network and theory of mind (ToM) network are related to individual differences in such emotion attenuation.