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Viral infections trigger complex immune responses with heterogeneous outcomes shaped by nonlinear feedback. A system of ordinary differential equations is developed to investigate immune response dynamics during viral infection, incorporating six modules, including viral load, innate immunity, cellular immunity, humoral immunity, immune suppression, and IL-6. Bifurcation analysis reveals that under continuous viral exposure, when viral clearance rate and intrinsic viral death rate satisfy specific conditions, the system exhibits up to five stable equilibria. This indicates that different health and disease states may coexist depending on initial conditions, while severe inflammation mainly arises from strong activation of cellular immunity, highlighting the complexity of immune responses. Simulations of finite-time viral exposure demonstrate multi-timescale recovery characteristics, with viral load and IL-6 levels declining rapidly, while humoral immune activation and immunosuppression show delayed and sustained patterns. Furthermore, analysis of infectious period and disease duration also indicates that during transition from early acute response to chronic disease, viral replication rate plays a critical role, while immune response intensity is sensitive to both viral clearance and immune self-activation. Subsystem analysis identifies the three-component subsystem of viral load, innate immunity, and cellular immunity as core drivers of bistability and oscillations, while humoral immunity, immune suppression, and IL-6 primarily modulate response amplitude and timing. This work establishes a theoretical framework for analyzing immune response and chronic risks through feedback dynamical modelling, providing insights for intervention strategies.

The Shaanxi section of the Qinling Mountains serves as a critical ecological transition zone and security barrier between northern and southern China. Monitoring the dynamics of its vegetation Net Primary Productivity (NPP) is essential for understanding regional carbon cycling and informing ecological management strategies. This study integrates three complementary analytical frameworks: the Mann–Kendall test combined with the Theil–Sen slope for linear trend extrapolation (MK-Theil-Sen), mechanistic simulation (CASA model), and machine learning (random forest). First, we analyzed the spatiotemporal evolution of NPP from 2000 to 2023. Then, based on three CMIP6 scenarios (SSP119, SSP245, SSP585), we projected NPP changes for 2030–2050 and compared results across different models and scenarios. The key findings are as follows: ① From 2000 to 2023, NPP in the Shaanxi section of the Qinling Mountains exhibited a fluctuating upward trend with a cumulative increase of 16.7%. Spatially, it showed a pattern of “higher in the south, lower in the north; higher in the west, lower in the east”. ② Multiple models predict continued NPP growth, though the magnitude remains uncertain. Mechanistic models, incorporating climate stress factors, yield relatively conservative projections. ③ Emission scenarios significantly influence future trends, with low-emission pathways (SSP119) favoring NPP enhancement and extended growing seasons. ④ Different vegetation types exhibit varying responses to scenario changes: broadleaf forests show the highest sensitivity, while grasslands and meadows demonstrate strong climate stability across models, with cultivated vegetation exhibiting intermediate sensitivity. This study provides comprehensive scientific references for regional ecological security assessment and adaptive management through historical analysis and multi-model, multi-scenario projections of NPP in the Shaanxi section of the Qinling Mountains.

Dendritic cells (DCs) play a crucial role in immune protection against myocardial infarction (MI). Through multiple experimental methods including bioinformatics, qPCR, Western blotting, immunofluorescence, MTT assays, echocardiography, TTC staining, and flow cytometry, this study found that metabolism was demonstrated to be markedly altered under oxygen–glucose deprivation (OGD) conditions in DCs. Pyruvate kinase M2 (PKM2) is a key protein in metabolism, and PKM2 was upregulated under OGD conditions in DCs. Trichostatin A (TSA) alleviated the OGD-induced cellular damage in DCs. Furthermore, TSA was shown to modulate DCs’ function by enhancing glycolysis while suppressing fatty acid synthesis and oxidation pathways. The metabolic changes caused by TSA and OGD were mechanistically mediated by PKM2. Mechanistically, PKM2 modulates glucose and lipid metabolism via its dimer formation. These results deepen our understanding of the interplay among TSA, glucose and lipid metabolism and DC functions in MI.

The quantum internet is a cutting‐edge paradigm that uses the unique characteristics of quantum technology to radically alter communication networks. This new network type is expected to collaborate with 6G networks, creating a synergy that will fundamentally alter how we communicate, engage, and trade information. The improved security, increased speed, and increased network capacity of the quantum internet will lead to the emergence of a broad variety of new applications and services. The current state of quantum technology and its integration with 6G networks are summarised in this study, with an emphasis on the key challenges and untapped possibilities. The main goal is to get knowledge about how the quantum internet might impact communication in the future and alter several economic and societal sectors. This review paper includes a comprehensive overview of the recently established quantum internet and 6G technologies, as well as a comprehensive introduction to the fundamental principles in these domains.

BackgroundNeutrophils-linked premetastatic niche plays a key role in tumor metastasis, but not much is known about the heterogeneity and diverse role of neutrophils in niche formation. Our study focuses on the existence and biological function of a rarely delved subset of neutrophils, named as tumor-associated aged neutrophils (Naged, CXCR4+CD62Llow), involved in premetastatic niche formation during breast cancer metastasis.MethodsWe explored the distributions of Naged in 206 patients and mice models (4T1 and MMTV-PyMT) by flow cytometry. The ability of Naged to form neutrophil extracellular traps (NETs) and promote tumor metastasis in patients and mice was determined by polychromatic immunohistochemistry, scanning electron microscopy and real-time video detection. Furthermore, the differences among tumor-associated Naged, Non-Naged and inflammation-associated aged neutrophils were compared by transcriptome, the biological characteristics of Naged were comprehensively analyzed from the perspectives of morphology, the metabolic capacity and mitochondrial function were investigated by Seahorse, co-immunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP) and transmission electron microscopy (TEM). Finally, 120 patients’ sample were applied to confirm the acceleration of Naged formation through secreted NAMPT, and the importance of blocking this pathway in mice was evaluated.ResultsWe find that Naged accumulate in the lung premetastatic niche at early stage of breast tumorigenesis in multiple mice models and also exist in peripheral blood and metastatic lung of patients with breast cancer. Naged exhibit distinct cell marker and morphological feature of oversegmented nuclei. Further transcriptome reveals that Naged are completely different from those of Non-Aged or inflammation-associated aged neutrophils and illustrates that the key transcription factor SIRT1 in Naged is the core to maintain their lifespan via mitophagy for their function. The responsible mechanism is that SIRT1 can induce the opening of mitochondrial permeability transition pore channels to release mitochondrial DNA and lead to the mitochondria-dependent vital NETs formation, rather than traditional Cit-Histone H3 dependent fatal-NETs. Further mechanically investigation found tumor derived NAMPT could induce Naged formation. Additionally, therapeutic interventions of Naged and its formation-linked pathways could effectively decrease breast cancer lung metastasis.ConclusionsNaged exerts a vital role in breast cancer lung metastasis, and strategies targeting SIRT1-Naged-NETs axis show promise for translational application.

The seagull optimization algorithm (SOA) is a meta-heuristic algorithm proposed in 2019. It has the advantages of structural simplicity, few parameters and easy implementation. However, it also has some defects including the three main drawbacks of slow convergence speed, simple search method and poor ability of balancing global exploration and local exploitation. Besides, most of the improved SOA algorithms in the literature have not considered the drawbacks of the SOA comprehensively enough. This paper proposes a hybrid strategies based algorithm (ISOA) to overcome the three main drawbacks of the SOA. Firstly, a hyperbolic tangent function is used to adjust the spiral radius. The spiral radius can change dynamically with the iteration of the algorithm, so that the algorithm can converge quickly. Secondly, an adaptive weight factor improves the position updating method by adjusting the proportion of the best individual to balance the global and local search abilities. Finally, to overcome the single search mode, an improved chaotic local search strategy is introduced for secondary search. A comprehensive comparison between the ISOA and other related algorithms is presented, considering twelve test functions and four engineering design problems. The comparison results indicate that the ISOA has an outstanding performance and a significant advantage in solving engineering problems, especially with an average improvement of 14.67% in solving welded beam design problem.

BackgroundAstrocytic activation might play a significant role in the central sensitization of chronic migraine (CM). However, the temporal characteristics of the astrocytic activation in the trigeminal nucleus caudalis (TNC) and the molecular mechanism under the process remain not fully understood. Therefore, this study aims to investigate the duration and levels change of astrocytic activation and to explore the correlation between astrocytic activation and the levels change of cytokines release.MethodsWe used a mice model induced by recurrent dural infusion of inflammatory soup (IS). The variation with time of IS-induced mechanical thresholds in the periorbital and hind paw plantar regions were evaluated using the von Frey filaments test. We detected the expression profile of glial fibrillary acidic protein (GFAP) in the TNC through immunofluorescence staining and western blot assay. We also investigated the variation with time of the transcriptional levels of GFAP and ionized calcium binding adapter molecule 1 (Iba1) through RNAscope in situ hybridization analysis. Then, we detected the variation with time of cytokines levels in the TNC tissue extraction and serum, including c-c motif chemokine ligand 2 (CCL2), c-c motif chemokine ligand 5 (CCL5), c-c motif chemokine ligand 7 (CCL7), c-c motif chemokine ligand 12 (CCL12), c-x-c motif chemokine ligand 1 (CXCL1), c-x-c motif chemokine ligand 13 (CXCL13), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), macrophage colony-stimulating factor (M-CSF), interleukin 1beta (IL-1β), interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 17A (IL-17A).ResultsRecurrent IS infusion resulted in cutaneous allodynia in both the periorbital region and hind paw plantar, ranging from 5 d (after the second IS infusion) to 47 d (28 d after the last infusion) and 5 d to 26 d (7 d after the last infusion), respectively. The protein levels of GFAP and messenger ribonucleic acid (mRNA) levels of GFAP and Iba1 significantly increased and sustained from 20 d to 47 d (1 d to 28 d after the last infusion), which was associated with the temporal characteristics of astrocytic activation in the TNC. The CCL7 levels in the TNC decreased from 20 d to 47 d. But the CCL7 levels in serum only decreased on 20 d (1 d after the last infusion). The CCL12 levels in the TNC decreased on 22 d (3 d after the last infusion) and 33 d (14 d after the last infusion). In serum, the CCL12 levels only decreased on 22 d. The IL-10 levels in the TNC increased on 20 d.ConclusionsOur results indicate that the astrocytic activation generated and sustained in the IS-induced mice model from 1 d to 28 d after the last infusion and may contribute to the pathology through modulating CCL7, CCL12, and IL-10 release.

Background Chronic stress promotes most hallmarks of cancer through impacting the malignant tissues, their microenvironment, immunity, lymphatic flow, etc. Existing studies mainly focused on the roles of stress-induced activation of systemic sympathetic nervous system and other stress-induced hormones, the organ specificity of chronic stress in shaping the pre-metastatic niche remains largely unknown. This study investigated the role of chronic stress in remodeling lung pre-metastatic niche of breast cancer. Methods Breast cancer mouse models with chronic stress were constructed by restraint or unpredictable stress. Expressions of tyrosine hydroxylase, vesicular acetylcholine transporter (VAChT), EpCAM and NETosis were examined by immunofluorescence and confocal microscopy. mRNA and protein levels of choline acetyltransferase (ChAT), VAChT, and peptidylarginine deiminase 4 were detected by qRT-PCR and Western blotting, respectively. Immune cell subsets were analyzed by flow cytometry. Acetylcholine (ACh) and chemokines were detected by ELISA and multi chemokine array, respectively. ChAT in lung tissues from patients was examined by immunohistochemistry. Results Breast cancer-bearing mice suffered chronic stress metastasized earlier and showed more severe lung metastasis than did mice in control group. VAChT, ChAT and ChAT + epithelial cells were increased significantly in lung of model mice undergone chronic stress. ACh and chemokines especially CXCL2 in lung culture supernatants from model mice with chronic stress were profoundly increased. Chronic stress remodeled lung immune cell subsets with striking increase of neutrophils, enhanced NETosis in lung and promoted NETotic neutrophils to capture cancer cells. ACh treatment resulted in enhanced NETosis of neutrophils. The expression of ChAT in lung tissues from breast cancer patients with lung metastasis was significantly higher than that in patients with non-tumor pulmonary diseases. Conclusions Chronic stress promotes production of CXCL2 that recruits neutrophils into lung, and induces pulmonary epithelial cells to produce ACh that enhances NETosis of neutrophils. Our findings demonstrate for the first time that chronic stress induced epithelial cell derived ACh plays a key role in remodeling lung pre-metastatic niche of breast cancer.

Background Sleep represents a key modifiable risk factor for cardiovascular diseases (CVDs). Although previous studies have examined separate associations of nighttime sleep duration and napping duration with CVDs, few have investigated their combined effects or elucidated how this association differs across age or gender. This study aimed to assess how different sleep combinations influence the CVD risk. Methods This study used longitudinal data from the China Health and Retirement Longitudinal Study (CHARLS) collected between 2011 and 2020. Baseline information on sleep and other relevant variables was obtained through self-reported questionnaires, and incident CVDs were identified during follow-up. Cox proportional hazards regression models were applied to evaluate independent and combined effects of nighttime sleep duration and napping duration on CVD incidence. Stratified analyses by age and gender explored potential heterogeneity, and sensitivity analyses were conducted to test result robustness. Results A total of 7,975 participants were included, of which 2,117 participants (26.55%) developed CVDs after follow up. After adjusting for confounders, insufficient nighttime sleep (< 6 h) was independently associated with a higher risk of CVDs (hazard ratio [HR]: 1.189, 95% confidence interval [CI]: 1.071–1.319). Compared with participants having moderate nighttime sleep without napping, those with < 6 h/night without napping (HR: 1.177, 95% CI: 1.021–1.357), < 6 h/night with napping duration ≤ 0.5 h (HR: 1.558, 95% CI: 1.236–1.962), and < 6 h/night with napping duration > 1 h (HR: 1.300, 95% CI: 1.020–1.655) had significantly higher CVD risk. Among these, the combination of < 6 h/night with napping duration ≤ 0.5 h was associated with the highest observed CVD incidence. Stratified analysis revealed significant heterogeneity by gender, with less pronounced associations between sleep combinations and CVD risk in men compared with those in women. Sensitivity analyses supported the robustness of findings. Conclusions Adequate nighttime sleep is associated with lower CVD risk. Most combinations of insufficient nighttime sleep and daytime nap increased CVD risk among middle-aged and older adults. However, the combination of insufficient nighttime sleep with moderate napping was not associated with increased CVD risk in this population. These results provide a scientific foundation for targeted sleep interventions and clinical guidance. Graphical Abstract

Mental fatigue refers to subjective feelings ranging from tiredness to exhaustion that appear after or during prolonged periods of cognitive activity. Music could be a powerful tool for relieving mental fatigue due to its beneficial effects on attention, which tend to decline when mental fatigue occurs. Moreover, traditional Chinese music is usually neglected and rarely used in music intervention studies, although its potential has been mentioned in China’s domestic journals. Therefore, the present study aimed to investigate the effects of traditional Chinese music and Western classical music on laboratory-induced mental fatigue. Three groups of Chinese non-psychology undergraduate students were assessed in terms of alertness, hedonic tone, and overall fatigue via a pre/post-intervention diary, a visual analogue mood scale, and the psychomotor vigilance test. The results showed that both traditional Chinese music and Western classical music mitigated fatigue-related declines in alertness and hedonic tone, and produced shorter reaction times, although there was no significant difference between the effects of the types of music.