Yi-Shen-Hua-Shi granules ameliorate renal injury via PPARγ-Klotho-mediated metabolic restoration and immune regulation in adenine-induced chronic kidney disease.

Spatiotemporal multi-omics profiling of secondary brain injury after intracerebral hemorrhage in an optimized autologous blood-induced mouse model with human tissue validation.

ECM-responsive nanomedicine to enhance immunotherapy in pancreatic cancer.

miRNA-149-5p protects endothelial function and attenuates sepsis-induced acute lung injury by targeting ABCA1.

Pulmonary arterial hypertension (PAH) is a fatal disease marked by pulmonary vascular remodeling. Although endothelial dysfunction and immune cell infiltration are central to its pathogenesis, the specific signaling mechanisms linking these elements remain unclear. This study investigates a novel pathway whereby endothelial cell-derived GM-CSF drives macrophage-dependent inflammation via the CCL2/CCR2 axis, ultimately promoting PAH progression through NLRP3 inflammasome activation. PAH mouse model was established using a high-fat diet (HFD) combined with L-NAME. Comprehensive in vivo assessments included echocardiography to evaluate cardiac function, Masson's Trichrome to measure vascular remodeling. In vitro, a co-culture system of mouse pulmonary arterial endothelial cells (MPAECs) and bone marrow-derived macrophages (BMDMs) was used, with palmitic acid (PA) stimulation to mimic PAH conditions. Key interventions involved administering a GM-CSF neutralizing antibody, depleting macrophages with clodronate liposomes, and utilizing Ccr2-/- mice. PAH mice exhibited significant pulmonary arterial wall thickening, right heart dysfunction, and increased lung wet-to-dry weight ratio. This was accompanied by early and sustained upregulation of GM-CSF and CCL2 in lung tissues, extensive infiltration of CCR2+ macrophages, and activation of the NLRP3 inflammasome cascade. In vitro, PA-stimulated MPAECs released GM-CSF, which promoted macrophage migration and CCL2 secretion, induced a pro-inflammatory M1 phenotype, and activated the NLRP3 pathway. Crucially, in vivo therapeutic interventions demonstrated that neutralizing GM-CSF, depleting macrophages, or knocking out Ccr2 all significantly alleviated PAH pathology. This study confirms that endothelial cell-derived GM-CSF promotes macrophage-NLRP3 inflammasome via the CCL2/CCR2 axis, thereby driving the progression of PAH. This axis may represent a promising therapeutic target for PAH.

COL11A2 Methylation as a Biomarker for Radiosensitivity and Microenvironment Remodelling in Oral Squamous Cell Carcinoma.

CXCL9 as a key feature for deep learning-based immune subtyping and prediction of immune checkpoint blockade response in triple-negative breast cancer.

Sjögren's disease (SjD) is a chronic, systemic autoimmune disease that mainly targets saliva- and tear-producing glands. T-cells are a substantial immune cell subset involved in SjD pathogenesis, including break of tolerance towardself, and constitute a major part of tissue-resident and infiltrating immune cells in salivary glands (SGs) of patients with SjD. CD4+ T-cells provide help to B-cells, thereby contributing to B-cell hyperactivity in this disease. Yet, interactions between T-cells and non-immune cells, including epithelial cells and fibroblasts, and how such interactions contribute to thedysfunction of the glands are incompletely understood. Although CD4⁺ T helper cells have long been a major focus of research due to their dominance within inflammatory foci and their role in B-cell differentiation, growing evidence also implicates CD8⁺ T-cells in pathogenic processes within SG tissue. In this review, novel findings regarding the role of T-cells in SjD pathogenesis are discussed, focusing on their phenotype and function in SGs. Furthermore, treatments targeting T-cells directly or indirectly that have demonstrated clinical efficacy in SjD are reviewed. Studying the impact of these treatments on T-cells may shed new light on their role in SjD pathogenesis.

The immune awakening: Transformative strategies against brain tumors.

Integrative bioinformatics identifies NSCLC biomarkers associated with LPS metabolism and circadian disruption.

The role of nitric oxide in skin inflammation and the pathogenesis of psoriasis.

Multi-omics profiling of ACOX3 unveils pan-cancer clinical biomarker potential.

Conventional radiotherapy compromises antitumor immunity through collateral damage to immune cells. While boron neutron capture therapy (BNCT) enables tumor-selective 10B (n, α) 7Li reactions, clinical agents like boronophenylalanine (BPA) suffer from excessive dosing and exhibit immune-metabolic inertia. We report a biomineralized albumin-based BNCT agent (Albumin@MnB) synthesized from clinically accessible borax, manganese, and albumin, which unlocks neutron capture-triggered immunotherapeutic activation. Albumin@MnB achieves potent tumor suppression at reduced boron doses, demonstrating superior efficacy compared with BPA. Importantly, Albumin@MnB enhances intratumoral immune cell infiltration and suppresses distant tumor growth, synergizing with adoptive T cell immunotherapy and immune checkpoint inhibitors. By integrating tumor-specific radiolytic energy deposition with metabolic reprogramming and immune activation, this strategy establishes boron neutron capture immunotherapy (BNCI) as a multimodal therapeutic paradigm that bridges targeted radiolysis with systemic antitumor immunity.

Engineered bacterial outer membrane vesicles enhanced tumor immunotherapy through remodeling tumor stroma and targeted delivery of CD73 siRNA.

The poor prognosis and high mortality rate of non‑small cell lung cancer are largely driven by its aggressive migratory and invasive behavior. Epithelial‑mesenchymal transition (EMT) is a central mechanism conferring these malignant traits. The present study examined the expression profile of the sodium channel β4 subunit (SCN4B) in lung adenocarcinoma (LUAD) and explored its regulatory role in EMT. Transcriptomic data from The Cancer Genome Atlas were analyzed to compare SCN4B expression between LUAD and normal tissues, and to assess its relationship with TNM clinical stage (I‑IV), overall survival and diagnostic performance using non‑parametric tests, Kaplan‑Meier analysis and receiver operating characteristic curves, respectively. Functional enrichment analysis, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and immune cell infiltration profiling were performed on SCN4B‑associated differentially expressed genes. In vitro, the A549 and H1299 LUAD cell lines were engineered to overexpress SCN4B. Viability, migration, invasion and apoptosis were evaluated using Cell Counting Kit‑8 assays, wound healing assays, Transwell assays and flow cytometry. In addition, western blotting was conducted to assess EMT markers, including E‑cadherin, N‑cadherin, Vimentin and Snail. The results demonstrated that SCN4B expression was markedly reduced in LUAD tissues and low SCN4B expression was associated with unfavorable clinical outcomes. KEGG analysis revealed enrichment of SCN4B‑related genes in the 'cell adhesion molecules' pathway, and SCN4B expression levels differed markedly between TNM tumor (T) pathologic stages T1 and T2. Furthermore, SCN4B overexpression suppressed viability, migration and invasion of A549 and H1299 cells, while promoting apoptosis. Western blotting demonstrated upregulation of E‑cadherin, and downregulation of N‑cadherin, Vimentin and Snail in the SCN4B overexpression group compared with the empty vector group, indicating inhibition of EMT. In conclusion, low SCN4B expression was associated with poor prognosis in LUAD. Notably, restoring SCN4B levels suppressed LUAD cell viability, migration and invasion in vitro, accompanied by inhibition of EMT. These findings highlighted SCN4B as a potential tumor suppressor and a promising therapeutic target for LUAD.

Lupenone regulates LOXL2-mediated PANoptosis signaling through E3 ubiquitin ligases RNF168 to improve radiation-induced lung injury.

Disorders in pulmonary vascular integrity are a prominent feature in many lung diseases. Paracrine signaling is highly enriched in the lung and plays a crucial role in regulating vascular homeostasis. However, the specific local cell-cell crosstalk signals that maintain pulmonary microvascular stability in adult animals and humans remain largely unexplored. In this study, we used single-cell RNA-sequencing-based computational pipelines to systematically profile ligand-receptor interactions within the lung microvascular niche and identified VEGF-D (vascular endothelial growth factor-D) as a key local factor with previously unrecognized barrier-protective properties in models of acute lung injury. Our single-cell RNA-sequencing data revealed that, under physiological conditions, soluble ligand-receptor interactions between mesenchymal cells, in particular alveolar fibroblasts, and microvascular endothelial cells are predominantly associated with pathways involved in maintaining vascular integrity as compared with all other cells. On treatment with top identified ligands, we found that VEGF-D significantly enhanced endothelial barrier function and conferred protection against inflammatory challenges induced by TNF-α (tumor necrosis factor-α), IL (interleukin)-1β, and thrombin. This barrier-protective effect of VEGF-D was significantly attenuated by inhibition of VEGFR2 (vascular endothelial growth factor receptor 2), either through siRNA knockdown or pharmacological blockade using specific VEGFR2 inhibitors. Intravenous administration of recombinant VEGF-D in lipopolysaccharide-induced acute lung injury models significantly reduced vascular permeability (7339±2510 a.u. [lipopolysaccharides] versus 5350±1821 a.u. [lipopolysaccharides+VEGF-D]; P<0.05), immune cell infiltration (0.791±0.199×106 whole blood cells/mL [lipopolysaccharides] versus 0.540±0.190×106 whole blood cells/mL [lipopolysaccharide+VEGF-D]; P<0.01), and the expression of proinflammatory markers TNF-α, IL-6, and keratinocyte chemoattractant in the lung tissue. This effect was abolished in VEGFR2iECKO (VEGFR2 inducible endothelial cells knockout) mice, confirming that VEGF-D mediates its effects via VEGFR2-dependent signaling. This study demonstrates an unexpected protective role for VEGF-D in promoting lung endothelial barrier integrity and suggests that paracrine signaling from the alveolar fibroblast niche contributes critically to lung capillary homeostasis.

Age-dependent reproductive decline has become a significant global health concern as the average maternal age at first birth increases. Fertility loss associated with reproductive aging is driven in part by alterations to ovarian composition and function, dysregulation of folliculogenesis, and increased inflammatory signaling. Our understanding of the molecular changes underlying ovarian aging has been expanded by single-cell and spatial transcriptomic studies, which identified infiltration of immune cells as a feature of ovarian aging. However, the function of these age-associated immune cells and their potential contributions to the inflammaging phenotype remain unclear. In this study, we integrate single-cell and spatial transcriptomics to define changes in the composition and intercellular signaling in the aging mouse ovary. We identify specific macrophage and T cell subpopulations that increase with age and are key sources of pro-inflammatory signaling in old ovaries. Further, we predict bidirectional signaling between these pro-inflammatory cells and granulosa cell populations that may impair follicular growth and development while promoting immune cell recruitment. These findings provide insights into the mechanisms that drive ovarian inflammaging.

Tumor immune cell infiltration plays an important role in determining treatment response and prognosis in colorectal cancer (CRC). This study aimed to investigate the association between tumor immune landscape and clinical outcomes in CRC patients receiving infusional 5-fluorouracil/leucovorin combined with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI)-based chemotherapy. Immune cell infiltration profiles were evaluated using transcriptomic data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the relative proportions of 22 immune cell subtypes were estimated using the CIBERSORTx algorithm. Associations between immune cell infiltration and treatment response, progression-free survival (PFS), and overall survival (OS) were systematically analyzed. A total of 511 CRC patients were included in the analysis. In patients receiving FOLFOX chemotherapy, improved drug response rates were positively associated with increased infiltration of M1 macrophages, whereas higher levels of gamma delta (γδ) T cells were correlated with poorer treatment response and reduced OS. In patients treated with FOLFIRI, elevated infiltration of M1 macrophages, M2 macrophages, activated natural killer (NK) cells, and T follicular helper (Tfh) cells was associated with unfavorable OS. Consensus clustering analysis identified three distinct immune subtypes, among which one subtype exhibited superior drug response rates and improved clinical outcomes following FOLFIRI treatment and was characterized by enrichment of adaptive immune cells, particularly memory CD4⁺ T cells and B cell-related populations. These findings demonstrate that specific immune cell subtypes and immunologically defined tumor subgroups are significantly associated with chemotherapy response and survival outcomes in CRC patients, highlighting the potential of tumor immune profiling as a predictive biomarker for chemotherapy efficacy.

To develop and validate a CT-based radiomics model to predict immunotherapy response in unresectable gastric cancer and explore its underlying biological mechanisms. This retrospective study included 368 unresectable gastric cancer patients receiving programmed death-1/programmed death ligand-1 (PD-1/PD-L1) inhibitors combined with chemotherapy from two centers. Patients were divided into training (n = 231), internal validation (n = 97), and external validation (n = 40) cohorts. Radiomics model was constructed using portal venous phase CT images, and a radiomics score (Radscore) was calculated for each patient. Five machine learning models incorporating clinical factors and Radscore were developed and compared. The best-performing model was used to construct a nomogram. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA). Immune cell infiltration analysis was performed using data from The Cancer Genome Atlas (TCGA) cohort. The radiomics signature, comprising 15 selected features, showed good predictive performance across all cohorts: training (AUC = 0.868), internal validation (AUC = 0.816), and external validation (AUC = 0.793). The logistic regression model demonstrated the highest and most consistent performance, with AUC values of 0.886, 0.831, and 0.826, respectively. The developed nomogram showed satisfactory calibration and clinical utility. Immune infiltration analysis revealed significant associations between Radscore and infiltration levels of activated CD4+ memory T cells, regulatory T cells, and CD8+ T cells. The CT-based radiomics nomogram showed promise for personalizing immunotherapy treatment strategies in unresectable gastric cancer. The association between the Radscore and immune cell infiltration provided insights into its biological basis. This rigorously validated CT radiomics nomogram critically advances gastric cancer immunotherapy prediction, offering clinical radiology a non-invasive, biologically-informed tool to guide personalized treatment decisions. CT radiomics provided a reliable marker for predicting gastric cancer immunotherapy response. The developed Radscore correlated with immune cell infiltration, offering biological insights. A nomogram integrating the Radscore and clinical factors showed robust predictive performance.