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The COVID-19 pandemic posed significant mental and physical challenges for healthcare professionals (HCPs), leading to increased stress and potential immune dysregulation. Yoga practice, has been suggested to enhance immunity and alleviate stress. This pilot study aimed to assess the impact of yoga intervention on immune markers, stress levels, and quality of life among HCPs actively working during the pandemic. A single-center, open label randomized controlled pilot study was conducted at tertiary care centre, with 36 participants. Physicians were randomly assigned to either a yoga intervention group (n=18) or a control group (n=18). The intervention included guided online yoga sessions for 12 weeks. Immunological markers (IL-6, IL-12, CRP, INF-gamma, TNF-alpha) were measured using ELISA at baseline and post-intervention. Stress levels and quality of life were assessed using the WHO-BREF questionnaire. Statistical analysis was performed Microsoft excel M365 software, employing t-tests. Significant improvements were observed in immune markers, particularly a reduction in IL-12 (p=0.0165) and CRP (p=0.001), alongside a marked increase in INF-gamma (p=0.001) in the yoga group. BMI significantly improved (p=0.0194), though stress levels and most quality-of-life domains remained unchanged, except for social relationships (p=0.0279). Correlation analysis suggested a strong relationship between BMI reduction and immune modulation. Yoga intervention demonstrated potential benefits in modulating immunological markers and improving BMI among physicians. While stress reduction was not significant, enhanced social relationships and immune function suggest yoga as a complementary approach for HCPs well-being during high-stress periods. Further large-scale studies are recommended to validate these findings.

Prostate cancer (PCa) remains a major clinical challenge due to therapeutic resistance and immunologically cold tumor microenvironment. Lysosomal membrane permeabilization (LMP)-induced lysosome-dependent cell death offers an alternative route to eliminate resistant tumor cells and initiate immunogenic cell death, yet its efficacy is often limited by insufficient spatiotemporal control and immune activation. Here, we report a spatiotemporally programmable supramolecular nanoplatform (Cu-P-MSA) that integrates lysosome-targeted sonodynamic therapy with tumor-confined innate immune activation for PCa treatment. Cu-P-MSA is a modular self-assembling peptide incorporating a PSMA-targeting ligand, morpholine moiety, and cathepsin B-cleavable linker, enabling tumor-selective uptake and in situ formation of fibrous sonosensitizer depots within lysosomes. Upon ultrasound irradiation, a glutathione-responsive open-shell sonosensitizer induces controlled LMP, simultaneously activating ferroptosis and pyroptosis and promoting immunogenic cell death. Meanwhile, tumor-specific release of a STING agonist MSA-2 elicits robust type I interferon responses, driving dendritic cell maturation and cytotoxic T-cell infiltration. This coordinated lysosomal disruption-immune amplification strategy effectively reprograms the tumor immune microenvironment and suppresses both primary and distant tumors, with inhibition rates reaching 84.3% and 77.5%, respectively. Overall, this work establishes a spatiotemporally controlled supramolecular approach that integrates lysosomal disruption with innate immune activation to overcome therapeutic resistance and immunosuppression in PCa.

Chronic kidney disease (CKD) is a major global health burden characterized by immune dysregulation. Peripheral blood lymphocyte subsets can reflect immune status across CKD pathologies. We evaluated associations between lymphocyte subsets and clinical parameters in patients undergoing renal biopsy in a contemporary cohort. We conducted a retrospective cross-sectional study of adults (≥16 years) who underwent native renal biopsy at Tongji Hospital, China, from January 2012 to December 2024. The lymphocyte subsets assessed by flow cytometry included combined T/B/NK cells (TBNK), total T cells (CD3+CD19-), total B cells (CD3-CD19+), helper T cells (CD3+CD4+), cytotoxic T cells (CD3+CD8+), and natural killer cells (CD3-CD16+CD56+). Clinical data included demographics, comorbidities, medications, and clinical and immunological markers. Multivariable linear regression was employed to investigate the relationships between lymphocyte subsets as continuous variables and clinical parameters, and nested regression using quartile categories to assess dose-response relationships. In total, 1,033 individuals were enrolled. TBNK levels declined with age (β = -4.33, 95% CI: -7.35 to -1.32) and were lower in females than males (β = -84.26, 95% CI: -157.29 to -11.23). Lymphocyte subset distributions varied by nephritis pathology: ANCA-GN and lupus nephritis showed lower levels than other types, whereas purpura nephritis was relatively higher. TBNK counts correlated positively with estimated glomerular filtration rate (β = 11.48, 95% CI: 6.78 to 16.19), with similar patterns for total B, total T, CD4+ T, and CD8+ T cells. Lymphocyte counts were also positively associated with complement 3. Among IgA nephropathy, TBNK levels correlated positively with IgA (β = 0.31, 95% CI: 0.06 to 0.57) and complement 3 (β = 0.10, 95% CI: 0.06 to 0.14). Lymphocyte and subset counts relate to renal function, immune indices, and pathology. Their measurement may help evaluate disease severity and immune status in nephritis and inform clinical management.

Systemic lupus erythematosus (SLE) is a prevalent autoimmune disease affecting up to a quarter million Americans. Lupus nephritis (LN) is an immune complex glomerulonephritis that occurs when circulating immune complexes deposit in the kidney and is a common sequela of SLE. LN serves as a marker of disease severity and contributes significantly to mortality in SLE. Despite growing access to novel therapies, the disease burden remains high, and the gap between real-life challenges and clinical trial success persists. Our study is an effort to bridge the gap by examining factors such as diverse choice of immunosuppression, socioeconomic constraints, and adherence outside the carefully calibrated environment of clinical trials. We conducted a retrospective review of patients with biopsy proven LN to evaluate prognostic factors and treatment related complications at a tertiary hospital with patients selected from biopsy records obtained from January 2015 through December 2023. A total of 66 patients met inclusion criteria and were included in the final analysis of the cohort. Patients with findings other than confirmed LN and kidney transplant recipients were excluded. Longitudinal data were collected at 6 months, 12 months, 2 years, and 5 years after biopsy, and response to treatment was defined using Kidney Disease Improving Global Outcomes (KDIGO) 2024 clinical practice guidelines for LN. Of the 163 kidney biopsy reports reviewed from January 2015 through December 2023, 66 were confirmed as LN and included in the analysis. The median age at biopsy was 35 years, 76% were women, and 62% were African American. At 6 months, 50% of Class I and II LN, 49% of Class III, IV, III + V and IV + V LN, and 83% of Class V LN had no response to treatment, without significant differences between classes or in terms of partial vs. complete response. At 12 months, 55% of Class I and II, 50% of Class III, IV, III + V, and IV + V, and 87% of Class V LN had no response to treatment, with a significant difference (p = 0.04) between classes in terms of rate of response, but not in terms of partial vs. complete response. Notable complications were advancement to ESRD in 11 patients (17%), infections that required hospital admission in 27 patients (41%), and death in 9 patients (14%) in the study period. Our study provides practical and real-world data on management of LN. In patients with SLE, LN is associated with significant morbidity and mortality. Management continues to pose a unique challenge despite developing therapies. Sustained remission is often dependent on a complex interplay of individualized care, patient adherence, and socioeconomic factors. There is a need for increased awareness of LN as early biopsy, prompt initiation and continuation of treatment positively impacts outcomes.

Timely recognition of immune checkpoint immune-related neurological adverse events (irNAEs) is critical given their potential severity, yet remains challenging due to limited clinical experience. This study investigates clinical presentation and management of irNAEs from a neurological perspective. We retrospectively identified all patients treated with immune checkpoint inhibitors (ICIs) at Erasmus MC Cancer Institute, Rotterdam, The Netherlands between 2017 and 2024. Patient records were analysed by a neurologist for clinical and treatment of irNAE post-ICI initiation. Of 3176 ICI-treated patients, irNAE was diagnosed in 76 cases (2.4%). Peripheral syndromes occurred in 55 (70%), central in 21 (30%) patients. Classification into distinct disease entities was challenging due to remarkable overlap in affected neurological structures. Median onset of irNAE was 8 weeks after ICI initiation (range 1-104 weeks); 70% developed within 18 weeks. IrNAE-related mortality was 13%, observed only in the first 18 weeks. Fewer non-small cell lung cancer patients developed irNAE (OR, 0.36; 95% CI 0.16 to 0.8; p=0.012) compared with other tumour types. Males (OR, 1.78; 95% CI 1.1 to 2.90; p=0.019) and PD1/CTLA4 combination therapy (OR 2.1, 95% CI 1.28 to 3.46, p=0.004) were associated with increased irNAE incidence. Glucocorticoids were given in 64% of patients; 14% received immunosuppressive therapy beyond steroids. Treatment response varied widely, both clinically and temporally. This retrospective single-centre study confirms irNAEs are infrequent complications of ICI. The distinct symptom profile, with substantial overlap within affected neurological structures, underscores the need for neurological expertise in irNAE care. While most develop within 18 weeks of treatment, late-onset cases occur. Mortality occurred only in early-onset cases.

Chicken infectious anemia virus (CIAV) is a major immunosuppressive pathogen of poultry, causing aplastic anaemia, lymphoid atrophy, and severe haematopoietic dysfunction in young chicks, thereby posing a substantial threat to global poultry health and production. In this study, a novel highly pathogenic CIAV strain, designated CIAV-GDHY230813, was isolated from young Mahuang chickens in China and subjected to comprehensive molecular and pathogenic characterization. Whole-genome sequencing and phylogenetic analysis revealed that CIAV-GDHY230813 belongs to I-a branch. Notably, the VP1 protein harbored a glutamine residue at position 394, a molecular marker strongly associated with high virulence, together with multiple amino acid substitutions, insertions, and deletions across the coding regions. Pathogenicity experiments in specific-pathogen-free (SPF) chicks demonstrated that infection with CIAV-GDHY230813 resulted in pronounced growth retardation, severe damage to immune organs, and increased mortality. From 3 to 21&#x202f;days post-infection (dpi), body weights of infected chicks were significantly lower than those of the control group (p <&#x202f;0.01). Marked thymic and bursal atrophy, splenomegaly, and significantly reduced haematocrit levels were observed, indicating severe anaemia. Furthermore, CIAV infection led to a marked reduction in antibody titres against Newcastle disease virus vaccination by 4-fold to 8-fold, reflecting substantial suppression of humoral immune responses. Quantitative analysis of viral distribution showed significantly elevated viral loads in blood, liver, thymus, spleen, and bursa of Fabricius at both 14 and 21 dpi (p&#x202f;<&#x202f;0.001), with peak levels detected at 21 dpi. Collectively, these findings demonstrate the strong replicative capacity and high pathogenic potential of CIAV-GDHY230813, providing valuable insights into the molecular epidemiology and pathogenic mechanisms of CIAV in China, supporting improved surveillance and control strategies, and laying a solid foundation for the development of effective vaccines against CIAV.

Recurrence-free survival (RFS) following radical prostatectomy is a pivotal measure of therapeutic success in prostate cancer (PCa), yet conventional clinicopathological tools offer limited discriminative accuracy. We sought to construct a platform-independent prognostic signature to predict RFS by capturing early molecular traces of advanced disease potential. Single-cell RNA sequencing data were analyzed to identify malignant epithelial subclusters and evaluate their compositional changes during the transition to castration-resistant prostate cancer (CRPC). We benchmarked 12 machine learning algorithms and 104 algorithmic combinations to develop a robust binary gene-pair signature in TCGA-PRAD cohort (n = 493) and validated in five external cohorts (n = 694). Downstream analyses included functional enrichment, immune and mutational profiling, drug sensitivity prediction and virtual knockouts. A 36-gene-pair signature was established, showing robust performance in predicting RFS across five external validation cohorts, with an average C-index of 0.725. Distinct signatures in signaling and metabolic processes were identified between the two risk groups through enrichment analysis. High-risk patients exhibited an immune-inflamed microenvironment with elevated TP53 mutation frequency and greater tumor mutational burden, and shared significant transcriptional similarities with responders to anti-PD-1 immunotherapy. These immunotherapy-related findings are hypothesis-generating and require prospective validation. Virtual knockout identified CKS2 as a risk-associated candidate gene linked to an androgen-responsive network, suggesting CKS2's potential role in the molecular reprogramming associated with PCa progression. The 36-gene-pair binary signature provides robust RFS risk stratification. High-risk individuals exhibit transcriptional similarity to reported anti-PD-1 therapy responders, and CKS2 emerges as a prognostic hub warranting validation.

Glioblastoma (GB) exhibits marked tumor microenvironmental heterogeneity, contributing to both therapy resistance and poor survival outcomes. Intercellular adhesion molecule 1 (ICAM1) is an inflammation-associated adhesion molecule implicated in immune-stromal interactions, but its clinical and biological significance in GB remains incompletely defined. We performed ICAM1 immunohistochemistry, bulk RNA sequencing, DNA methylation analysis, single-nucleus RNA sequencing, and preoperative MRI-derived morphologic feature analysis across multi-institutional cohorts of treatment-na&#xef;ve IDH-wildtype GB. High ICAM1 expression at both transcript and protein levels is associated with shorter overall survival, particularly within the mesenchymal transcriptional subtype. ICAM1 expression is inversely associated with promoter methylation. Single-nucleus RNA-sequencing analysis shows that ICAM1-high tumors are enriched for mesenchymal, hypoxia, stress-associated, and immunosuppressive myeloid programs, suggesting that ICAM1 reflects a multicompartment inflammatory tumor ecosystem. ICAM1 expression, tumor surface irregularity, and patient age are independently prognostic and minimally correlated, capturing complementary clinical, imaging, and molecular features of GB biology. When combined, our Clinical-Imaging-Molecular (CIM) framework refines outcome prediction across independent GB cohorts using routinely available clinical data, conventional imaging, and standard immunohistochemistry. ICAM1 characterizes an immune-remodeled, stress-adapted GB ecosystem associated with poor clinical outcomes. Integrating patient age, surface irregularity, and ICAM1 expression yields a scalable and clinically accessible prognostic framework for GB, supporting tailored outcome prediction, particularly in low- and middle-resource settings without routine access to advanced molecular profiling.

Rhabdomyolysis is characterized by skeletal muscle breakdown resulting in the release of intracellular contents into the circulation. Although trauma, medications, and metabolic disorders are common causes, viral infections are increasingly recognized as potential triggers. A 26-year-old previously healthy male presented with a 2-day history of abdominal pain, diarrhea, vomiting, bilateral thigh pain, and dark urine. Laboratory evaluation demonstrated severe rhabdomyolysis with a peak creatine phosphokinase (CK) level of 25,036 U/L, elevated aminotransferases, and preserved renal function. A stool gastrointestinal multiplex polymerase chain reaction (PCR) panel was positive for adenovirus and did not identify other enteric pathogens. Alternative etiologies, including significant recent exertion, medication-related muscle injury, toxin exposure, autoimmune myopathy, and inherited metabolic disorders, were considered but were not supported by the clinical history or disease course. The patient was treated with early intravenous isotonic fluid 1L every 6 hours and experienced progressive biochemical and clinical improvement without developing acute kidney injury. Adenovirus-associated rhabdomyolysis is an uncommon but increasingly recognized clinical entity in adults. The pathogenesis may involve direct viral muscle injury, immune-mediated inflammation, and contributory factors such as dehydration associated with gastrointestinal illness. Although adenovirus was considered the most likely precipitating factor in this case, a definitive causal relationship cannot be established. This case highlights probable adenovirus-associated rhabdomyolysis in an immunocompetent young adult presenting predominantly with gastrointestinal symptoms and preserved renal function despite marked creatine kinase elevation. Early recognition, careful evaluation of alternative etiologies, and prompt supportive management are important for preventing complications and achieving favorable outcomes.

Pathogenic immune-cardiac crosstalk underlies maladaptive remodeling in chronic heart failure, yet therapies directly targeting this axis are lacking. Glycoconjugates, which are crucial for signal transduction and extracellular matrix integrity, represent an underexploited therapeutic avenue. This study sought to define the role of glycoconjugate-metabolizing enzymes at the immune-cardiac interface and evaluate their translational potential. We performed integrative analyses of bulk and single-cell RNA sequencing data from failing human and mouse hearts. Employing mouse models of pressure overload (transverse aortic constriction) and ischemia-reperfusion, we used global and mast cell (MC)-specific gene deletion, bone-marrow chimeras, and pharmacological neutralization. Mechanistic insights were gained through multiomics profiling, including RNA-seq, ATAC-seq, CUT&Tag, and proteomics. The ganglioside GD3 synthase, St8sia1, was selectively induced in cardiac MCs during pathological remodeling in both mice and humans. MC-specific or hematopoietic deletion of St8sia1 preserved ventricular function, attenuated fibrosis, and markedly reduced neutrophil and Ly6C+ monocyte recruitment after transverse aortic constriction and ischemia-reperfusion. Therapeutic neutralization of GD3 with the clinical-grade monoclonal antibody R24 improved cardiac function and diminished scar formation after ischemia-reperfusion. Mechanistically, GD3 bound specific histone variants, such as H2A.Z and H3.3C, thereby reprogramming chromatin accessibility to activate proinflammatory and profibrotic transcriptional programs in MCs. Consequently, GD3 inhibition suppressed MC degranulation, disrupted pathogenic MC-cardiomyocyte/fibroblast crosstalk, and preserved reparative macrophage populations. The MC-restricted St8sia1-GD3 axis functions as a glyco-epigenetic checkpoint driving maladaptive cardiac remodeling. Targeting this axis represents a translatable immunomodulatory strategy to prevent the progression to chronic heart failure.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by progressive destruction of insulin-producing &#x3b2;-cells, resulting in lifelong insulin dependence and impaired quality of life. Although a transient phase of partial remission may occur after diagnosis, sustained preservation of &#x3b2;-cell function remains exceptional. Recently, low-carbohydrate diets (LCD) have gained attention among patients, partly driven by anecdotal reports describing prolonged remission. The aim of this review was to critically examine the existing clinical evidence for prolonged partial remission under LCD in patients with T1DM and to summarize the biological mechanisms proposed in the literature to explain such observations. A literature review was conducted focusing on reports of prolonged remission in individuals with T1DM adopting an LCD, as well as experimental studies exploring mechanistic pathways potentially modulated by carbohydrate restriction. Only six individual cases describing prolonged partial remission under LCD were identified in the literature. The diagnostic certainty of T1DM in these reports was variable, and misclassification (eg, latent autoimmune diabetes in adults or monogenic diabetes) cannot be excluded. The mechanistic hypotheses proposed-including reduction of glucotoxicity, modulation of inflammation, attenuation of oxidative stress, and possible &#x3b2;-cell regeneration-are derived predominantly from animal models, in vitro studies, and non-T1DM populations. Currently, no controlled clinical trial has demonstrated that LCDs prolong remission or preserve &#x3b2;-cell function in patients with T1DM. Evidence supporting prolonged partial remission under LCD in patients with T1DM remains based on rare case reports of uncertain diagnostic validity. Mechanistic data are largely indirect and extrapolated from heterogeneous experimental contexts. At present, LCD cannot be considered as a therapeutic strategy for inducing or maintaining remission in T1DM. This review highlights the need for well-designed longitudinal studies with stringent diagnostic criteria and mechanistic validation in authentic T1DM models.

Uveal melanoma (UM) is a challenging malignancy, in terms of diagnosis, risk stratification, and treatment associated with high morbidity and mortality rates. It has been demonstrated that E2F-related pathways play a significant role in the tumorigenesis and distant metastasis of UM. In this study, the E2F target-related genes were utilized to construct and validate a prognostic risk score for patients with UM. Using the TCGA-UVM cohort (n = 80), 192 E2F target genes were screened using gene set enrichment analysis (GSEA) to identify survival-associated genes. Prognostic genes were filtered using Kaplan-Meier analysis, univariate Cox regression, and LASSO, followed by multivariate Cox regression to construct a risk score model. The model was validated using the GSE22138 cohort (n = 63). Functional annotations of the risk score and its impact on stratifying tumor immune microenvironment components were assessed. A total of 9 genes (CDC25B, NME1, RFC2, PRDX4, NASP, UBE2S, PRKDC, MCM6, and LBR) passed the model construction pipeline. The risk score categorization system showed an independent prognostic power (HR: 2.34, 95% CI: 1.11-4.90, p = 0.025) and a good predictability of the survival outcome (receiver operating characteristic curve analysis: area under the curve = 0.730, 95% CI: 0.60-0.86, p = 0.002). When analyzing the most frequently mutated gene cohorts, the risk score was significantly lower in the mutated subgroups of GNAQ, SF3B1, and EIF1AX. In contrast, the risk score was notably higher in the BAP1 mutated subgroup. Copy number analysis of chromosomal arms showed significant correlations between the risk score and 1q, 3q, 3p, 6p, 8q. The high-risk group showed significant infiltration for NK cells, plasma B cells, gamma delta T cells, follicular T cells, M1 and M2 macrophages with lower infiltration of common myeloid progenitor cells. In addition, the high-risk group showed higher immune and microenvironment scores. The developed E2F target-related gene model offers a robust tool for predicting the prognosis of UM patients. As a potential risk stratification method for UM, this model could have clinical applications pending further evaluation.

To identify predictive metabolic biomarkers for immune-related adverse events (irAEs) in cancer patients treated with immune checkpoint inhibitors (ICIs) using metabolomics, supporting early detection and intervention. Fifty-five ICI-treated cancer patients from Changxing People's Hospital were divided into irAEs-positive (34 cases) and irAEs-negative (21 cases) groups after 12-month follow-up. Pretreatment serum samples were analyzed by untargeted UPLC-MS metabolomics. PCA, OPLS-DA, and KEGG pathway enrichment were used to screen differential metabolites and key pathways. Seventy significant differential metabolites (eg, ursodeoxycholic acid, uric acid) were identified. &#x3b2;-Alanine metabolism, pentose phosphate pathway, and coenzyme A biosynthesis were closely correlated with irAEs. Five metabolites showed AUC 0.7-0.9 with favorable predictive performance. Metabolomics reveals specific metabolites and metabolic pathways linked to ICI-induced irAEs, providing potential biomarkers for early prediction and new insights into irAEs pathogenesis to optimize clinical management.

Pandalus hypsinotus (P. hypsinotus), also known as coonstripe shrimp, has high economic value and is widely distributed in Alaska, the Bering Sea and the East Sea of Korea. However, owing to the low catch rates and patchy spatial distribution, transcriptome-based studies on this species remain limited. Transcriptome analyses using PacBio Iso-Seq and Illumina RNA sequencing techniques were performed to establish a de novo unigene set of P. hypsinotus and identify differentially expressed genes (DEGs) in the hepatopancreas compared to the tail muscle. A search of all the unigenes against Gene Ontology (GO), KEGG, Pfam, BLASTN, and UniProt resulted in 46,703 annotated unigenes. A comparison of the sequences in the two tissue-derived libraries revealed 9,429 DEGs in the hepatopancreas. We also investigated the small RNAomes of P. hypsinotus using the Illumina small RNA sequencing technology. Because miRNAs are highly sensitive to stress responses and pathogen infections, they serve as effective indicators of the immune status, thereby acting as crucial tools for enhancing productivity and disease control in the aquaculture industry. The 130 identified microRNA (miRNA) candidates were classified into 32 orthologous and 98 novel miRNAs using BLASTN and miRBase. Through GO analysis and direct interactions between miRNAs and genes, the differentially expressed miRNAs (DEMs) and DEGs related to immune responses showed regulatory relationships based on their sequences. These findings provide a valuable resource for future studies on novel gene detection, gene mapping and biological pathways that may be regulated by miRNAs unique to P. hypsinotus.

Chronic cough, particularly prevalent in post-COVID condition (PCC, also known as long COVID), remains a significant medical challenge. Recently, extracellular vesicles (EVs) have gained significant attention for their therapeutic potential. In this study, we explore the therapeutic effects of EVs derived from mesenchymal stem cells (MSCs) cultured in a 3D system (3D-EVs) in treating chronic cough, with a focus on post-COVID-19 patients. Our in vitro experiments demonstrated that 3D-EVs promote angiogenesis and cell migration, crucial processes in tissue repair and regeneration. Notably, 3D-EVs exhibited a robust suppressive effect on lymphocyte proliferation in human PBMCs, indicating their potential immunomodulatory role. At day 6, nebulized 3D-EVs treatment group showed significantly higher rates of significant improvement (22.5% vs. 5.0%, P = 0.023) and total effectiveness (67.5% vs. 47.5%, P = 0.035), as well as a shorter mean time to cough resolution (13.83 vs. 19.90 days, P = 0.037). By day 14, total effective rates were comparable (85% vs. 80%, P > 0.05). No safety concerns were observed. RNA sequencing revealed altered B cell receptor signaling and downregulation of the mitotic cell cycle pathway, while exploratory immunophenotyping identified a significant reduction in plasma cells (P < 0.05) and directional trends in other immune subsets, providing preliminary evidence that 3D-EVs may modulate B cell differentiation and immune responses. These findings demonstrate the feasibility and preliminary efficacy of 3D-EVs for rapid relief of post-COVID-19 chronic cough, supporting larger controlled trials to validate their role in this and related respiratory diseases.

Cancer-related lymphedema is a chronic progressive side effect of cancer treatments followed by lymph node dissection or radiotherapy. Clinicians often identify lymphedema through limb swelling, while the disease begins earlier than that. Lymphatic injury is the original cause, where elevated interstitial fluid pressure and distorted tissue mechanics will lead to immune activation and fibrofatty remodeling. Recently, mechanobiology studies have deepened our understanding by linking lymph stasis to T helper 2/transforming growth factor &#x3b2; signaling, fibroblast mechanotransduction, and YAP/TAZ activity that together lock tissues into a stiff, poorly draining state. Simultaneously, emerging artificial intelligence (AI) in the field are being explored, from proof-of-concept image classification to much more diagnostic models that integrate elastography, indocyanine green lymphography, radiomics, clinical variables, and wearable signals to detect preclinical mechanical signatures and predict risk. These advances are driving the development of promising mechanomedical approaches, such as adaptive compression systems, AI-assisted plans for lymphatic reconstruction, anti-fibrotic strategies, and lymphangiogenic regeneration, although most remain at preclinical or early clinical feasibility stages of translation. We discuss the strength of current evidence, challenges for clinical translation, and standards for reporting. We propose that cancer-related lymphedema can be understood as a measurable and targetable mechano-immune-fibrotic disease, for which AI may eventually support earlier diagnosis, risk prediction, and personalized mechanotherapy.

Cryoglobulinemic vasculitis is an immune-complex-mediated small-vessel vasculitis characterized by complement activation and endothelial injury. Its clinical manifestations are heterogeneous and may range from limited cutaneous involvement to systemic disease. We report the case of a 65-year-old woman who developed a symmetrical violaceous dermatosis involving the upper and lower extremities, accompanied by arthralgias and distal paresthesias. Laboratory investigations revealed marked hypocomplementemia and positive circulating cryoglobulins. Histopathological examination of a skin biopsy demonstrated leukocytoclastic vasculitis, leading to the diagnosis of idiopathic cryoglobulinemic vasculitis after exclusion of hepatitis C virus infection, autoimmune diseases, and associated hematologic malignancies, with no evidence of major systemic organ involvement. Treatment with corticosteroid- and cyclophosphamide-based immunosuppression achieved sustained disease control, resulting in approximately 90% symptomatic improvement. This case highlights the importance of recognizing cardinal manifestations, such as palpable purpura, arthralgias, and hypocomplementemia, when evaluating patients with suspected cryoglobulinemic vasculitis, even in the absence of identifiable secondary causes. Early recognition, histopathological confirmation, and a multidisciplinary approach are essential for establishing an accurate diagnosis and implementing timely therapeutic intervention aimed at preventing disease progression and irreversible organ damage.