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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.
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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.
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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.
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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.
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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.
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Azoospermia , Proteínas del Grupo de Complementación de la Anemia de Fanconi , Transducción de Señal , Animales , Humanos , Masculino , Azoospermia/genética , Azoospermia/metabolismo , Azoospermia/patología , Daño del ADN , Reparación del ADN , Proteínas del Grupo de Complementación de la Anemia de Fanconi/metabolismo , Proteínas del Grupo de Complementación de la Anemia de Fanconi/genética , EspermatogénesisRESUMEN
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.
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Electroencefalografía , Semántica , Humanos , Encéfalo/fisiología , Interfaces Cerebro-Computador , China , Lenguaje , Lingüística , Procesamiento de Lenguaje Natural , LecturaRESUMEN
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.
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Comprensión , Individualidad , Imagen por Resonancia Magnética , Red Nerviosa , Lectura , Humanos , Comprensión/fisiología , Masculino , Femenino , Adulto Joven , Adulto , Red Nerviosa/fisiología , Red Nerviosa/diagnóstico por imagen , Lenguaje , Mapeo Encefálico , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Red en Modo Predeterminado/fisiología , Red en Modo Predeterminado/diagnóstico por imagen , ConectomaRESUMEN
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.
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Enfermedades Renales , Insuficiencia Renal Crónica , Rheum , Obstrucción Ureteral , Ratas , Animales , Factor de Crecimiento Transformador beta1/metabolismo , Rheum/metabolismo , Regulación hacia Abajo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Transducción de Señal , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/etiología , Enfermedades Renales/metabolismo , Riñón/patología , Obstrucción Ureteral/metabolismo , Obstrucción Ureteral/patología , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patología , Fibrosis , Autofagia , ARN Mensajero/metabolismoRESUMEN
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.
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Isquemia Encefálica , Electroacupuntura , Accidente Cerebrovascular Isquémico , Daño por Reperfusión , Accidente Cerebrovascular , Animales , Ratones , Isquemia Encefálica/terapia , Isquemia Encefálica/metabolismo , Electroacupuntura/métodos , Infarto de la Arteria Cerebral Media/terapia , Infarto de la Arteria Cerebral Media/metabolismo , Enfermedades Neuroinflamatorias , Daño por Reperfusión/metabolismo , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/metabolismo , Canales Catiónicos TRPV/genéticaRESUMEN
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.
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Electroencefalografía , Percepción Social , Humanos , Potenciales Evocados/fisiología , Encéfalo/fisiología , Aislamiento SocialRESUMEN
[This corrects the article DOI: 10.3389/fphar.2021.621359.].