Although global brain science research has progressed rapidly in recent decades, several fundamental questions in neuroscience remain unresolved. In particular, the physical mechanism underlying neural signal transmission remains controversial, and the carriers responsible for neural information storage and retrieval have not yet been fully clarified. These unresolved issues motivate us to re-examine the processes of neural information generation, transmission, integration, storage, and retrieval from multiple perspectives. A key observation is that neural electromagnetic activities are closely associated with time. Their duration, temporal structure, and dynamic evolution play crucial roles in neural information processing. In this work, we analyze neural electromagnetic activities from the perspective of temporal scales (referred to here as the “time course”). By reviewing and integrating findings from previous studies, we examine the characteristic time requirements and dynamic features of neural processes occurring at different stages of information processing. These stages include neural signal generation, signal transmission along axons, synaptic integration, synaptic plasticity, and memory formation and retrieval. Based on this temporal analysis, we outline a framework describing neural electromagnetic activities across a wide range of time scales, spanning from microseconds to minutes, hours, or even longer periods associated with long-term memory, which suggests that neural information processing involves multiple physical processes operating at different time levels. Rapid electromagnetic events may occur on microsecond scales, whereas electrophysiological phenomena such as action potentials typically last on the order of milliseconds. Longer time scales are associated with synaptic plasticity and memory-related processes. From this perspective, we propose that the physical carrier of neural information may be transient electromagnetic pulses with durations on the microsecond scale. In this framework, action potentials can be interpreted as the macroscopic electrophysiological manifestation of underlying electromagnetic processes triggered by ionic currents across neuronal membranes. Rather than being the fundamental neural signal itself, the action potential may represent a measurable membrane-level response associated with the successful activation of these electromagnetic events. Moreover, we discuss a possible mechanism for long-term memory storage. Considering the apparent temporal contradiction between the millisecond-scale excitation of neurons and the long-term persistence of memories, we believe that long-term memory information may be stored within neural network topologies formed by electrical synapse coupling. Such structures, referred to as electrically coupled memory networks (ECMNs), may enable neurons within the same network to respond rapidly and synchronously to stimuli, thereby facilitating efficient memory retrieval. Overall, this study emphasizes the importance of considering the temporal organization of neural electromagnetic activities when interpreting neural signaling mechanisms. It may provide new insights into the physical nature of neural information carriers and the mechanisms of memory storage and retrieval. Furthermore, highlighting the potential role of electromagnetic interactions in neural activity may contribute to the development of new theoretical frameworks and experimental approaches in neuroscience. Such perspectives may also offer valuable references for future research on neural coding, brain function mechanisms, and neuromodulation technologies.

Objective To develop and validate a transgenic mouse model enabling specific and inducible optogenetic activation of oligodendrocyte precursor cells(OPCs).Methods A conditional allele for the photosensitive opsin chicken opsin 5(cOpn5)(Rosa26-LSL-cOpn5)was generated using CRISPR/Cas9 technology.These mice were subsequently crossed with NG2-CreERT transgenic mice to produce NG2-CreERT;cOpn5 animals.In this model,tamoxifen administration induces Cre-mediated recombination,leading to specific expression of cOpn5 in NG2-positive OPCs.The specificity and efficiency of cOpn5 expression in OPCs were confirmed by immunofluorescent staining.Functional validation of light-induced OPC activation was performed by using calcium imaging in acute brain slices after stimulation with 470 nm blue light.Results Immunofluorescence analysis confirmed robust and specific expression of cOpn5 within NG2-positive OPCs in the brains of tamoxifen-treated NG2-CreERT;cOpn5 mice.Crucially,calcium imaging of acute brain slices from these mice demonstrated a significant increase in intracellular calcium levels in cOpn5-expressing OPCs upon stimulation with 470 nm blue light,indicating successful optogenetic activation.Conclusion We have successfully generated and validated a novel transgenic mouse model(NG2-CreERT;cOpn5)that permits specific and inducible optogenetic activation of OPCs.This model provides a novel tool for subsequent in vivo studies of the role and regulating mechanisms of OPCs in the central nervous system.

Objective:To investigate the correlation between postoperative perceived stress,quality of life and fear of cancer recurrence(FCR)in elderly non-small-cell lung cancer(NSCLC)patients.Methods:This study was a prospective research design,a total of 147 elderly NSCLC patients who visited Shanxi Integrated Traditional Chinese and Western Medicine Hospital from January 2023 to June 2024 were prospectively selected for the study.All patients underwent thoracoscopic lobectomy.FCR in patients was evaluated by fear of disease progression simplified scale(FoP-Q-SF),and they were divided into dysregulation group and non dysregulation group according to the FoP-Q-SF score.Quality of life was evaluated by functional assessment of cancer therapy-lung cancer(FACT-L).Perceived stress was evaluated by Chinese version of the perceived stress scale(CPSS)score.The scores of postoperative perceived stress,quality of life and postoperative FCR in elderly NSCLC patients were analyzed,and the influence of demographic and clinical characteristics on the postoperative FCR in elderly NSCLC patients.The postoperative perceived stress and quality of life scores of elderly NSCLC patients with different FCR were compared,the correlation between postoperative FCR and perceived stress and quality of life in elderly NSCLC patients were analyzed,as well as the model fitting index of the influence of postoperative perceived stress and quality of life on FCR in elderly NSCLC patients.Results:The postoperative CPSS score in elderly NSCLC patients was(52.17±4.02)points,the FACT-L score was(80.39±4.56)points,and the total score of FoP-Q-SF was(31.16±8.69)points.Family relationship,economic burden of disease,chemotherapy and clinical stage were closely associated with the postoperative FCR in elderly NSCLC patients(P＜0.05).The CPSS score in dysregulation group was higher than that in nondysregulation group,and the FACT-L score was lower than that in nondysregulation group(P＜0.05).Pearson correlation analysis,postoperative FCR in elderly NSCLC patients was positively correlated with perceived stress,but negatively correlated with quality of life(P＜0.05).The postoperative quality of life in elderly NSCLC patients was recorded as the independent variable,the postoperative perceived stress was recorded as the mediating variable,and the postoperative FCR was recorded as the dependent variable,a structural model of the mediating effect was routinely constructed.The results showed that the model fits well.Quality of life had a direct negative predictive effect on postoperative FCR in elderly NSCLC patients(P＜0.05),and could affect FCR through postoperative perceived pressure(P＜0.05),with the mediating effect accounting for 34.15％of the total effect.After repeatedly sampling the data using the Bootstrap method and implementing the mediating effect,the 95％CI of each model path did not include 0,indicating that the difference in the mediating effect was statistically significant(P＜0.05).Conclusion:Postoperative FCR in elderly NSCLC patients is positively correlated with perceived stress,but negatively correlated with quality of life,clinically,monitoring such indicators can be considered to better evaluate the postoperative FCR in elderly NSCLC patients.

Objective To develop and validate a transgenic mouse model enabling specific and inducible optogenetic activation of oligodendrocyte precursor cells(OPCs).Methods A conditional allele for the photosensitive opsin chicken opsin 5(cOpn5)(Rosa26-LSL-cOpn5)was generated using CRISPR/Cas9 technology.These mice were subsequently crossed with NG2-CreERT transgenic mice to produce NG2-CreERT;cOpn5 animals.In this model,tamoxifen administration induces Cre-mediated recombination,leading to specific expression of cOpn5 in NG2-positive OPCs.The specificity and efficiency of cOpn5 expression in OPCs were confirmed by immunofluorescent staining.Functional validation of light-induced OPC activation was performed by using calcium imaging in acute brain slices after stimulation with 470 nm blue light.Results Immunofluorescence analysis confirmed robust and specific expression of cOpn5 within NG2-positive OPCs in the brains of tamoxifen-treated NG2-CreERT;cOpn5 mice.Crucially,calcium imaging of acute brain slices from these mice demonstrated a significant increase in intracellular calcium levels in cOpn5-expressing OPCs upon stimulation with 470 nm blue light,indicating successful optogenetic activation.Conclusion We have successfully generated and validated a novel transgenic mouse model(NG2-CreERT;cOpn5)that permits specific and inducible optogenetic activation of OPCs.This model provides a novel tool for subsequent in vivo studies of the role and regulating mechanisms of OPCs in the central nervous system.

Objective:To investigate the correlation between postoperative perceived stress,quality of life and fear of cancer recurrence(FCR)in elderly non-small-cell lung cancer(NSCLC)patients.Methods:This study was a prospective research design,a total of 147 elderly NSCLC patients who visited Shanxi Integrated Traditional Chinese and Western Medicine Hospital from January 2023 to June 2024 were prospectively selected for the study.All patients underwent thoracoscopic lobectomy.FCR in patients was evaluated by fear of disease progression simplified scale(FoP-Q-SF),and they were divided into dysregulation group and non dysregulation group according to the FoP-Q-SF score.Quality of life was evaluated by functional assessment of cancer therapy-lung cancer(FACT-L).Perceived stress was evaluated by Chinese version of the perceived stress scale(CPSS)score.The scores of postoperative perceived stress,quality of life and postoperative FCR in elderly NSCLC patients were analyzed,and the influence of demographic and clinical characteristics on the postoperative FCR in elderly NSCLC patients.The postoperative perceived stress and quality of life scores of elderly NSCLC patients with different FCR were compared,the correlation between postoperative FCR and perceived stress and quality of life in elderly NSCLC patients were analyzed,as well as the model fitting index of the influence of postoperative perceived stress and quality of life on FCR in elderly NSCLC patients.Results:The postoperative CPSS score in elderly NSCLC patients was(52.17±4.02)points,the FACT-L score was(80.39±4.56)points,and the total score of FoP-Q-SF was(31.16±8.69)points.Family relationship,economic burden of disease,chemotherapy and clinical stage were closely associated with the postoperative FCR in elderly NSCLC patients(P＜0.05).The CPSS score in dysregulation group was higher than that in nondysregulation group,and the FACT-L score was lower than that in nondysregulation group(P＜0.05).Pearson correlation analysis,postoperative FCR in elderly NSCLC patients was positively correlated with perceived stress,but negatively correlated with quality of life(P＜0.05).The postoperative quality of life in elderly NSCLC patients was recorded as the independent variable,the postoperative perceived stress was recorded as the mediating variable,and the postoperative FCR was recorded as the dependent variable,a structural model of the mediating effect was routinely constructed.The results showed that the model fits well.Quality of life had a direct negative predictive effect on postoperative FCR in elderly NSCLC patients(P＜0.05),and could affect FCR through postoperative perceived pressure(P＜0.05),with the mediating effect accounting for 34.15％of the total effect.After repeatedly sampling the data using the Bootstrap method and implementing the mediating effect,the 95％CI of each model path did not include 0,indicating that the difference in the mediating effect was statistically significant(P＜0.05).Conclusion:Postoperative FCR in elderly NSCLC patients is positively correlated with perceived stress,but negatively correlated with quality of life,clinically,monitoring such indicators can be considered to better evaluate the postoperative FCR in elderly NSCLC patients.

This study was aimed at exploring the interaction between the nucleoprotein(NP)of influenza A virus(IAV)and TRIM25.The physicochemical properties and protein structure of IAV NP protein were analyzed through bioinformatics methods.The interaction between IAV NP and TRIM25 proteins was simulated with molecular docking techniques,and the in-teraction sites were predicted.With the cDNA of the A/Puerto Rico/8/1934(H1N1)PR8 strain as the template,the NP pro-tein was cloned into the eukaryotic expression vector pCMV-C-Flag through PCR amplification,the eukaryotic expression re-combinant plasmid pCMV-Flag-NP was constructed,and the expression was further verified.The protein expression levels of pCMV-Flag-NP and pCMV-HA-TRIM25 were detected at various time periods.The interaction between NP protein and TRIM25 protein was verified by co-immunoprecipitation.The co-localization of NP protein and TRIM25 protein in cells was ob-served with laser confocal microscopy.Bioinformatics analysis revealed that the NP protein consists of 498 amino acids and 20 amino acids,and is an unstable hydrophilic protein.The NP protein has multiple phosphorylation sites,as well as N-glycosyla-tion and O-glycosylation sites,but no transmembrane domain or signal peptide domain.Additionally,the NP protein's second-ary structure consists of a high proportion of alpha-helices and random coils.The molecular docking prediction results indicated that IAV NP interacts with TRIM25 protein and has multiple potential interaction sites,including the 233rd alanine,234th ala-nine,236th lysine,and 440th alanine of the NP protein.After successfully constructing and expressing the IAV NP protein,we verified the interaction between IAV NP and TRIM25 protein by immunoprecipitation and laser confocal microscopy obser-vations.Our results together suggested that the structure of the IAV NP protein is closely related to its function,and its im-portance to the virus is clear.In addition,the interaction between IAV NP and TRIM25 protein may be associated with TRIM25's anti-influenza virus mechanism.Further in-depth research may provide new ideas for anti-influenza virus strategies.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Hemorrhagic shock is a common clinical emergency that can aggravate cell injury after resuscitation. Astrocytes are crucial for the survival of neurons because they regulate the surrounding ionic microenvironment of neurons. Although hemorrhagic shock and resuscitation (HSR) injury can impair cognition, it remains unclear how this insult directly affects astrocytes. In this study, we established an HSR model by bleeding and re-transfusion in mice. The social interaction test and new object recognition test were applied to evaluate post-operative cognitive changes, and the results suggest that mice experience cognitive impairment following exposure to HSR. In the HSR group, the power spectral density of β and γ oscillations decreased, and the coupling of the θ oscillation phase and γ oscillation amplitude was abnormal, which indicated abnormal neuronal oscillation and cognitive impairment after HSR exposure. In brief, cognitive impairment in mice is strongly correlated with Ca²⁺ signal strength in lateral septum astrocytes following HSR.
Animals ; Astrocytes/metabolism* ; Shock, Hemorrhagic/metabolism* ; Resuscitation/adverse effects* ; Male ; Mice ; Calcium Signaling/physiology* ; Mice, Inbred C57BL ; Septal Nuclei/metabolism* ; Cognitive Dysfunction/etiology* ; Disease Models, Animal ; Cognition Disorders/etiology*

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*