Search Results (296)

Background/Objectives: Angioimmunoblastic T-cell lymphoma (AITL) is a rare peripheral T-cell lymphoma of follicular helper T-cell (TFH) origin, often associated with immune dysregulation and EBV-positive B-cell proliferation. Kaposi sarcoma (KS) is a vascular neoplasm caused by human herpesvirus 8 (HHV-8), typically arising in immunocompromised individuals. The synchronous occurrence of AITL and KS in HIV-negative patients is exceptionally rare, with only three cases previously reported worldwide. Case Presentation: We describe an 81-year-old HIV-negative Korean woman presenting with progressive generalized edema and dyspnea. Imaging revealed multifocal lymphadenopathy. Excisional biopsy of the inguinal lymph node showed two distinct but adjacent neoplastic processes. The AITL component demonstrated a polymorphous infiltrate of atypical TFH cells expressing CD3, CD4, CD10, PD-1, and Bcl-6, with monoclonal TCR-γ rearrangement and TET2 and RHOA mutations. The KS component comprised spindle cells with slit-like vascular spaces, red blood cell extravasation, and immunoreactivity for HHV-8, CD31, CD34, and ERG. The findings were consistent with a collision tumor. Despite supportive care, the patient’s condition deteriorated, and she was discharged with palliative care. Discussion: The coexistence of AITL and KS in an HIV-negative setting raises important pathogenetic considerations. AITL is characterized by profound immune dysregulation, with depletion of normal T-cell subsets, abnormal B-cell activation, and cytokine milieu changes that may favor latent viral reactivation. This immunologic environment may permit HHV-8 reactivation, thereby facilitating the development of KS even in the absence of overt immunodeficiency due to HIV infection. Our findings support the hypothesis that AITL-related immune dysfunction may create a permissive niche for HHV-8-driven neoplasia. Conclusions: This is the first reported case in Asia and the fourth worldwide of a collision tumor comprising AITL and KS in an HIV-negative patI dient. The case suggests that AITL-associated immune dysregulation may facilitate HHV-8 reactivation and KS development even in the absence of HIV infection. Awareness of this association is critical for accurate diagnosis and optimal patient management. Full article

This paper develops a dynamic information-theoretic network framework to quantify systemic risk in China’s maritime–commodity nexus with a focus on the Yangtze River Basin using eight monthly indicators, CCFI, CBCFI, BDI, YRCFI, GAUP, MPCT, CPUS, and ASMC. We resample, impute, standardize, and difference series to achieve stationary time series. Nonlinear interdependencies are estimated via KSG mutual information (MI) within sliding windows; networks are filtered using the Planar Maximally Filtered Graph (PMFG) with bootstrap edge validation (95th percentile) and benchmarked against the MST. Average MI indicates moderate yet heterogeneous dependence (about 0.13–0.17), revealing a container/port core (CCFI–YRCFI–MPCT), a bulk/energy spine (BDI–CPUS), and commodity bridges via GAUP. Dynamic PMFG metrics show a generally resilient but episodically vulnerable structure: density and compactness decline in turbulence. Stress tests demonstrate high redundancy to diffuse link failures (connectivity largely intact until ∼70–80% edge removal) but pronounced sensitivity of diffusion capacity to targeted multi-node outages. Early-warning indicators based on entropy rate and percolation threshold Z-scores flag recurring windows of elevated fragility; change point detection evaluation of both metrics isolates clustered regime shifts (2015–2016, 2018–2019, 2021–2022, and late 2023–2024). A Systemic Importance Index (SII) combining average centrality and removal impact ranks MPCT and CCFI as most critical, followed by BDI, with GAUP/CPUS mid-peripheral and ASMC peripheral. The findings imply that safeguarding port throughput and stabilizing container freight conditions deliver the greatest resilience gains, while monitoring bulk/energy linkages is essential when macro shocks synchronize across markets. Full article

When considering an urban agglomeration as a unit, promoting the coupling and coordination of the land price gradient and industrial gradient is crucial for achieving regional integrated development. We selected the Beijing–Tianjin–Hebei Urban Agglomeration (BTHUA) as a case study; constructed a three-dimensional analytical framework involving static coupling, dynamic coupling, and spatial matching; theoretically clarified the coupling mechanism between the land price gradient and industrial gradient; and systematically assessed their spatial-temporal patterns and coupling characteristics. The results indicate that from 2012 to 2022, both the land price gradient and industrial gradient within the BTHUA exhibited a “core-periphery” spatial distribution, gradually forming an over-all pattern of “one core, multiple nodes, and multi-level rings.” For the Beijing–Tianjin–Hebei urban agglomeration, overall static coupling and spatial matching exhibit an evolutionary trajectory of “first rising, then declining.” By contrast, dynamic coupling remains relatively weak, exhibiting a corridor-shaped distribution along core and sub-core cities. All three indicators consistently show that core cities outperform peripheral cities. Nonlinear mechanism analysis based on the gradient boosting decision tree method showed that “second-nature” factors like economic development and public utilities significantly promote multidimensional coupling. Conversely, “first-nature” factors, such as geographic conditions, have limited impacts with threshold effects; surpassing these thresholds results in inhibitory effects. Based on the research findings, this study proposes that regional integration should serve as the guiding principle, emphasizing the cultivation of regional development corridors, the implementation of flexible and functionally aligned land supply policies, the strengthening of land use performance audits, and the reorientation of fiscal and financial policies toward structural and qualitative improvements. These measures can provide valuable references for promoting coordinated industrial development and balanced land allocation in urban agglomerations. Full article

Background: Various studies have demonstrated fucoidan’s immunomodulatory effects. A previous study reported the anticancer effects of Durvillaea antarctica fucoidan (DAF) via immune activation in mice. Methods: In this study, we confirmed the DAF’s pulmonary immune activation ability by nasal administration of the dendritic cells (DCs) and T cells. Furthermore, we examined its ability to enhance the efficacy of lung cancer treatment by combining it with anti-PD-L1 antibodies to activate the lung immune response. Results: Nasal DAF administration increased C-C chemokine receptor type 7 expression in DCs and promoted DC migration to the mediastinal lymph nodes (mLN). Specifically, DAF increased conventional DC type 1 (cDC1) and cDC2 numbers in mLN and potently activated cDC1. Furthermore, the nasal administration of DAF increased the production of inflammatory cytokines in the lungs and peripheral blood. Repeated intranasal administration of DAF induced T-cell activation, resulting in the enhanced production of interferon-gamma and tumor necrosis factor-alpha in CD4 T and CD8 T cells. CD8 T cells also showed increased secretion of cytotoxic mediators after DAF treatment, and the proportion of Tregs expressing FoxP3 decreased in the mLN. DAF inhibited lung cancer growth in Lewis lung carcinoma 2 cells, which was enhanced by combining it with an anti-programmed death-ligand 1 antibody. Finally, the anticancer effects of DAF were not observed in mice with depleted CD4-positive and CD8-positive cells. Conclusions: Nasal administration of DAF may inhibit lung cancer growth by inducing lung immune activation and is expected to be helpful as an immune activator for nasal administration. Full article

Values remain notoriously difficult to “capture” because they cannot be directly observed. Attitudes and opinions are the only known indicators of their presence. The relationship between values and attitudes or opinions is that between latent and manifest, so that values can be justifiably inferred from observed attitudes and expressed opinions. Nevertheless, this is an epistemological limitation to reckon with. So, the alternative we propose is to explore cultural values as an integral part of social representations. We want to show that social representation theory can help with identifying values in an accurate and reliable manner. It is only due to the fact that we already have a common representation of social reality that we can develop attitudes that can then be manifested by expressing opinions. If values directly intervene in the formation of attitudes, they will surely be part of the representations that triggered that formation in the first place. Using a mixed-method approach, professionals’ representations of their professional role were explored in order to identify the values associated with it. As cognitively processed cultural constructs, values can be identified as elements of the central node of professionals’ representation of their profession. Full article

Carbon flow tracking and spatial pattern optimization at the scale of urban functional zones are key scientific challenges in achieving carbon neutrality. However, due to the complexity of carbon metabolism processes within urban functional zones, related studies remain limited. To address these scientific challenges, this study, based on the “source–sink–flow” ecosystem services framework, develops an integrated analytical approach at the scale of urban functional zones. The carbon balance is quantified using the CASA model in combination with multi-source data. A network model is employed to trace carbon flow pathways, identify critical nodes and interruption points, and optimize the urban spatial pattern through a low-carbon land use structure model. The research results indicate that the overall carbon balance in Hangzhou exhibits a spatial pattern of “deficit in the center and surplus in the periphery.” The main urban area shows a significant carbon deficit and relatively poor connectivity in the carbon flow network. Carbon sequestration services primarily flow from peripheral areas (such as Fuyang and Yuhang) with green spaces and agricultural functional zones toward high-emission residential–commercial and commercial–public functional zones in the central area. However, due to the interruption of multiple carbon flow paths, the overall carbon flow transmission capacity is significantly constrained. Through spatial optimization, some carbon deficit nodes were successfully converted into carbon surplus nodes, and disrupted carbon flow edges were repaired, particularly in the main urban area, where 369 carbon flow edges were restored, resulting in a significant improvement in the overall transmission efficiency of the carbon flow network. The carbon flow visualization and spatial optimization methods proposed in this paper provide a new perspective for urban carbon metabolism analysis and offer theoretical support for low-carbon city planning practices. Full article

Nomadic heritage villages constitute significant material cultural heritage. Under China’s cultural revitalization and rural development strategies, these villages face spatial degradation driven by tourism and urbanization. Current research predominantly employs isolated analytical approaches—space syntax often overlooks social dynamics while social network analysis (SNA) overlooks physical interfaces—hindering the development of holistic solutions for socio-spatial resilience. This study proposes a multi-scale integrated assessment framework combining social network analysis (SNA) and space syntax to systematically evaluate public space structures in traditional nomadic villages of Xinjiang. The framework provides scientific evidence for optimizing public space design in these villages, facilitating harmonious coexistence between spatial functionality and cultural values. Focusing on three heritage villages—representing compact, linear, and dispersed morphologies—the research employs a hierarchical “village-street-node” analytical model to dissect spatial configurations and their socio-functional dynamics. Key findings include the following: Compact villages exhibit high central clustering but excessive concentration, necessitating strategies to enhance network resilience and peripheral connectivity. Linear villages demonstrate weak systemic linkages, requiring “segment-connection point supplementation” interventions to mitigate structural elongation. Dispersed villages maintain moderate network density but face challenges in visual integration and centrality, demanding targeted activation of key intersections to improve regional cohesion. By merging SNA’s social attributes with space syntax’s geometric precision, this framework bridges a methodological gap, offering comprehensive spatial optimization solutions. Practical recommendations include culturally embedded placemaking, adaptive reuse of transitional spaces, and thematic zoning to balance heritage conservation with tourism needs. Analyzing Xinjiang’s unique spatial–social interactions provides innovative insights for sustainable heritage village planning and replicable solutions for comparable global cases. Full article

As the cradle of Jiangnan culture, Suzhou is home to a dense concentration of historical architectural heritage that is currently facing existential threats from rapid urbanization. This study aims to develop a spatial heritage corridor network for conservation and sustainable utilization. Using kernel density estimation, this study identifies 15 kernel density groups, along with the Analytic Hierarchy Process (AHP), to pinpoint clusters of historical architectural heritage and assess the involved resistance factors. Current Effective Conductance (CEC) theory is further applied to model spatial flow relationships among heritage nodes, leading to the delineation of 27 heritage corridors and revealing a spatial structure characterized by one primary core, one secondary core, and multiple peripheral zones. Based on 15 source points, six cultural relics-themed routes are proposed—three land-based and three waterfront routes—connecting historical sites, towns, and ecological areas. The study further recommends a resource management strategy centered on departmental collaboration, digital integration, and community co-governance. By integrating historical architectural types, settlement forms, and ecological patterns, the research builds a multi-scale narrative and experience system that addresses fragmentation while improving coordination and sustainability. This framework delivers practical advice on heritage conservation and cultural tourism development in Suzhou and the broader Jiangnan region. Full article

This study examines the impact of the Beijing–Tianjin–Hebei (BTH) coordinated development policy on the regional industrial network structure, with a focus on the significance of electricity consumption data in social network analysis (SNA). Utilizing a gravity model integrated with electricity consumption data, this research employs centrality analysis and Lambda analysis to compare changes in the steel industry network before and after policy implementation. The findings reveal that traditional models relying solely on indicators such as population and Gross Domestic Product (GDP) fail to comprehensively capture regional economic linkages, whereas incorporating electricity consumption data enhances the model’s accuracy in identifying core nodes and latent connections. Post policy implementation, the centrality of Beijing and Tianjin increased significantly, reflecting their transition from production hubs to centers for research and development (R&D) and management, while Shijiazhuang’s pivotal role diminished. This study also uncovers a “core–periphery” structure in the BTH urban network, where core cities (Beijing, Tianjin, and Shijiazhuang) dominate resource allocation and information flow, while peripheral cities exhibit uneven development. These results provide a scientific basis for optimizing regional coordinated development policies and underscore the critical role of electricity consumption data in refining regional economic analysis. Incorporating electricity consumption data into the gravity model significantly enhances its explanatory power by capturing hidden economic ties and improving policy evaluation, offering a more accurate and dynamic assessment of regional industrial linkages. Full article

Streptococcus suis (S. suis) is a major pathogen in pigs and an emerging zoonotic agent which causes serious infections in humans. It is also an immunosuppressive pathogen that exerts detrimental effects on the thymus, spleen, lymph nodes, and macrophages, impairing their ability to perform their normal physiological functions. S. suis induces thymic atrophy, splenomegaly, and lymphadenectasis and triggers apoptosis in T cells and B cells, as well as pyroptosis in macrophages within immune organs. Subsequently, T cell subsets in peripheral blood become abnormal, and the expression of cytokines becomes dysregulated, which leads to host immunosuppression, suggesting a new virulence mechanism of S. suis. Full article

Background/Objectives: Breast cancer (BC) is a multifactorial disease, with genetic alterations in cell proliferation and migration pathways being significant risk factors. This study examines the association between three variants in the BIRC5 gene (rs8073069, rs17878467, and rs9904341) and breast cancer (BC) susceptibility. Methods: Peripheral blood DNA samples were collected from 423 women (221 BC patients and 202 healthy controls). Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) methodology. Associations were calculated using odds ratios (OR), with p-values adjusted by the Bonferroni test (significance at p ≤ 0.016). In silico analyses were conducted to predict the functional impact of the analyzed variants. Results: Patients carrying the C/C genotype for the rs8073069 variant showed increased susceptibility to BC with early TNM (tumor-node-metastasis classification) stage and Luminal A subtype (OR > 2.00; p ≤ 0.004). For the rs17878467 variant, patients with the C/T or T/T genotype exhibited a higher susceptibility to developing breast cancer (BC), particularly at early TNM stages or with a histological lobular type (OR > 2.00; p ≤ 0.012). Regarding the rs9904341 variant, patients with the G/C or C/C genotype had a higher susceptibility to breast cancer. Notably, G/C genotype carriers with Luminal A and B subtypes, and C/C genotype carriers who had TNM stages II and III, and Luminal A, Luminal B, and HER2 subtypes demonstrated increased risk (OR > 2.00; p ≤ 0.009). The C-T-C haplotype (rs8073069–rs17878467–rs9904341) was significantly associated with BC (OR = 4.20; 95% CI = 2.38–7.41; p ≤ 0.001). In silico analysis using CADD indicated a low probability of deleterious effects. Conclusions: The results suggest that the rs8073069, rs17878467, and rs9904341 variants in BIRC5 have a significant influence on breast cancer susceptibility. Full article

Dendritic cells (DCs) play a central role in the immunopathogenesis of rheumatoid arthritis (RA), yet their regulation by tumor necrosis factor alpha (TNF) and associated receptors remains poorly characterized. We applied a single-cell multi-omics approach (CITE-seq) to profile peripheral blood mononuclear cells (PBMCs) from RA patients and healthy donors, before and after in vitro TNF stimulation. Using integrated analysis of surface protein expression and transcriptomic data, we focused on phenotypic and transcriptional changes in dendritic cell populations. DCs from RA patients exhibited elevated surface expression of CD14 and CD16, indicative of an inflammatory phenotype, and showed marked responsiveness to TNF. Upon stimulation, RA-derived DCs upregulated genes involved in antigen presentation (CD83, LAMP3), lymph node migration (CCR7, ADAM19), and inflammation (TRAF1, IL24) whereas such activation was absent in healthy controls. Our data reveal a TNF-responsive, pro-inflammatory transcriptional program in dendritic cells from RA patients and underscore the relevance of the TNF receptor profile in shaping DC function. These findings provide new insights into the immunobiology of RA and identify dendritic cells as potential targets for personalized immunomodulatory therapy. Full article

Background/Objectives: While the presence of inflammatory processes in stenotic aortic valves is acknowledged, no systematic characterization of the systemic immune reaction upon aortic valve stenosis (AS) has been performed yet. The hypothesis of this study was that AS induces a systemic inflammatory reaction linked with local processes in the heart. Methods: Murine wire injury (WI) to induce AS, or sham surgery, were performed prior to the 4-week assessment of AS severity, left ventricular (LV) function and hypertrophy with echocardiography (echo). Organ weights, levels of leukocytes, cytokines and costimulatory molecules in blood, heart, and peripheral immune organs (spleen, liver, lymph nodes), and immune cell uptake of Cy5-labelled perfluorocarbon nanoemulsions were measured. Results: Trends towards correlation were found between organ weights, myocardial immune cells and echo. Cytokine mRNA levels trended mainly towards an increase in heart and regional lymph nodes and a reduction in spleen and liver, and correlation with echo was more homogeneous after WI. Unchanged cytokine protein levels in myocardium and plasma trended to correlate with echo. A homogeneous pattern was found for echo and costimulatory molecule correlation, while PFC uptake by lymphatic cells was reduced upon AS. Conclusions: The results suggest a link between number and activation state of leukocytes in peripheral organs and cardiac processes in AS. Considering the pathological value of inflammation, it is crucial that future studies investigate if a modulation of the systemic inflammatory reaction relieves severity of AS and opposes development of heart failure. Full article

Background and Objectives: Mantle cell lymphoma (MCL) is a highly heterogenous disease, but an optimal prognostic biomarker in relapsed/refractory (R/R) MCL has not yet been established. The circular RNA-based risk score, circSCORE, was recently proposed as a promising prognosticator in newly diagnosed, younger patients with MCL. This study explores the prognostic potential of circSCORE in R/R MCL in both nodal (lymph node (LN)) and non-nodal tissues (bone marrow (BM)) and peripheral blood (PB)). Materials and Methods: RNA was extracted from 65 relapse samples consisting of first-relapse LN samples (n = 20) from patients who previously underwent first-line treatment in the MCL2 and MCL3 trials, and either BM (n = 34) or PB (n = 11) samples obtained from patients with R/R MCL included in the MCL6 trial, taken at trial baseline. Kaplan–Meier estimates, and Cox regressions were used to evaluate the association between circSCORE risk groups (high versus low) and outcomes. Results: Survival analyses showed significantly inferior outcomes for patients with high-risk circSCORE compared to low-risk score for both progression-free survival (PFS) (hazard ratio (HR) 1.99, p-value 0.0407) and overall survival (OS) (HR 2.29, p-value 0.0192) in the total cohort. The same tendencies were displayed when exploring the non-nodal samples only. Furthermore, circSCORE retained prognostic impact for PFS, but not OS, when adjusted for Ki67, MIPI, and TP53 mutation status. Conclusions: The circRNA-based risk score, circSCORE, displayed prognostic potential in R/R MCL along with promising application in non-nodal tissues, indicating that circSCORE, if further validated, might serve as an easily obtainable biomarker in R/R MCL. Full article

Background/Objectives: The prevalence of lung cancer in patients with a peripheral pulmonary nodule referred for navigation bronchoscopy (NB) is high. Combining NB with a systematic EBUS for staging is common practice. We investigated the added value of performing EBUS in the population referred for NB in relation to the available pre-procedural [¹⁸F]FDG-PET and CT imaging information. Methods: This single-center study evaluated all consecutive patients who underwent an NB in an academic referral center. [¹⁸F]FDG-PET and CT scoring of lymphadenopathy was based on routine [¹⁸F]FDG-PET and/or contrast-enhanced chest (ce) CT imaging reports and were correlated to outcome of systematic EBUS and subsequent surgery (when available). Results: In total, 403 patients were included for analysis of which 327 underwent EBUS (81.1%). In 138/403 patients (35%) who had positive lymph nodes on [¹⁸F]FDG-PET (86.5%) or ceCT (13.5%), 12 lung cancer patients were diagnosed with N+ disease by EBUS (8.4%). An additional nine EBUS-negative patients were diagnosed with N+ disease after surgery (5.4%). In the group of patients with imaging-negative lymph nodes (65.8%), no metastatic lymph nodes were found by EBUS, and surgery revealed occult nodal metastasis in eight patients (3.1%). Conclusions: In patients with peripheral pulmonary nodules referred for NB, EBUS may be safely omitted when [¹⁸F]FDG-PET or ceCT imaging does not indicate presence of nodal involvement. Full article