Endogenous Retroviruses (ERVs) are originated from ancient exogenous viruses, which integrate into the host genome after infection and persist across all vertebrate lineages. Complete ERV consists of viral genes (gag, pro, pol, and env) in the center and two Long Terminal Repeats (LTRs) at both ends, which encode viral structural proteins, critical enzyme, and glycoprotein. ERVs constitute approximately 8% of human genome and function in a wide range of physiological and pathological processes, including embryonic development, inflammation and infection, neurodegenerative diseases, cancers, etc. The expression of ERVs is controlled mainly by epigenetic modification, transcriptional regulation and post-transcriptional modulation, which offered important therapeutic targets. In this review, we reviewed the structure and function of ERVs, summarized recent research advances on how ERVs contribute to cancer initiation and progression, and introduced some therapies targeting ERVs.

Tumor-associated macrophages (TAMs) are key regulators of immune homeostasis within the tumor microenvironment (TME) and play critical roles in malignant progression. However, the molecular mechanisms linking macrophage metabolic remodeling to immune regulation remain incompletely understood. Glycine cleavage system H protein (GCSH), a core regulator of copper-dependent cell death, has been implicated in metabolic regulation in triple-negative breast cancer (TNBC), suggesting a potential role in macrophage-mediated TME remodeling.

We integrated single-cell RNA sequencing and spatial transcriptomic data from TNBC tissues to systematically characterize macrophage subpopulations with high GCSH expression. Pseudotime trajectory analysis, cuproptosis-related scoring, cell-cell communication inference, metabolic pathway enrichment, and spatial localization analyses were performed to delineate their functional heterogeneity and microenvironmental context. In addition, mutation profiling, immunogenomic analysis, drug sensitivity prediction, and in vitro and in vivo functional experiments were conducted to comprehensively evaluate the biological and therapeutic relevance of GCSH.

GCSH expression was predominantly enriched in macrophages, particularly in early activated subsets, and was associated with enhanced amino acid and lipid metabolic activity. GCSH + macrophages exhibited extensive interactions with T cells via pathways such as MIF-CD74-CXCR4 and LGALS9-CD45, contributing to an immunosuppressive, tumor-promoting microenvironment. Spatial analysis revealed their preferential localization at the tumor core-stroma interface. Notably, GCSH missense mutations were associated with increased M1 macrophage infiltration and enrichment of immune and inflammatory pathways. Clinically, high GCSH expression correlated with poor survival, genomic instability, and chemotherapy resistance. Functional experiments demonstrated that GCSH silencing suppressed tumor cell proliferation, migration, and clonogenicity, induced apoptosis, enhanced proinflammatory cytokine secretion, and significantly inhibited tumor growth in vivo.

GCSH acts as a central molecular link between macrophage metabolic reprogramming, immune suppression, and TNBC progression, highlighting its potential as both a prognostic biomarker and therapeutic target.

Cell-cell interactions influence gene expression in the tumor microenvironment, yet despite advances in spatial transcriptomics that enable in situ expression profiling, current computational tools remain limited in quantitatively resolving single-cell and multicellular interaction effects across patient tissues. Here, we present InSituPREP (In Situ Proximity Expression Programs), a computational framework for quantifying how spatial context relates to transcriptional states in three-dimensional tissues at single-cell resolution. The framework quantifies proximity-associated gene programs across multiple analytical layers. We applied InSituPREP to Expansion Sequencing data from breast cancer biopsies of 10 patients, integrating newly generated and previously published datasets and profiling 299 cancer-related genes. This analysis revealed that a portion of within-cell type variability reflects proximity-associated transcriptional states, that proximity-dependent programs are reproducible across patients and measurement platforms, and that spatial RNA velocity links intercellular distance to future transcriptional trajectories. Linear modeling showed that gene expression in specific cell types varies with intercellular distance and the number of neighboring cells, while triplet configurations revealed additional interaction-associated programs. Moreover, simultaneous detection of bacterial signals and host mRNA enabled us to link bacterial proximity to distinct transcriptional responses. InSituPREP provides a framework for quantifying spatially associated gene expression and dissecting context-dependent transcriptional states at single-cell resolution.

The Src-like adaptor 2 (SLA2) functions as a negative regulator of T cell receptor signalling. However, its involvement in the tumour microenvironment (TME) of gastric cancer (GC) remains unexplored. In this study, we found that SLA2 expression was significantly elevated in GC tissues, and a high level of SLA2 was associated with poor prognosis in GC patients. Bioinformatics analyses revealed a close association between SLA2 and TME in GC. Single-cell RNA sequencing analysis indicated that SLA2 was significantly enriched in CD8⁺ T cells in GC tissues. Functional validation demonstrated that SLA2 overexpression contributed to the exhaustion of CD8⁺ T cells by suppressing their proliferation, upregulating the expression of exhaustion markers, reducing the secretion of effector cytokines (IFN-γ and TNF-α) and impairing cytotoxic function. SLA2 knockdown in in vitro-generated exhausted CD8 T cells significantly alleviated T cell exhaustion. Mechanistically, we found that inverse promoter methylation and active histone marks (H3K27ac, H3K4me3 and H3K4me1) may regulate SLA2 expression. Our findings suggest that SLA2 may modulate the TME and promote immune evasion via CD8⁺ T cell exhaustion in GC.

Ovarian cancer is a particularly lethal malignancy often diagnosed at advanced stages, highlighting the urgent need for novel therapeutic strategies. This study investigates the expression and functional role of LINC00240, miR-30c-5p, and P4HA2 in ovarian cancer pathogenesis. Using datasets GSE66957 and the GEPIA database, we assessed LINC00240 expression levels and employed quantitative real-time polymerase chain reaction (qRT-PCR) to evaluate the expression of LINC00240, miR-30c-5p, and P4HA2 in ovarian cancer samples. Bioinformatics analysis via TargetScan software predicted interactions between these molecules, which were validated through dual-luciferase reporter assays. Functional assays, including colony formation and Transwell assays, assessed the impact of LINC00240 and miR-30c-5p on cell proliferation, migration, and invasion. Our results indicate that LINC00240 and P4HA2 are significantly overexpressed, while miR-30c-5p is downregulated in ovarian cancer. Furthermore, LINC00240 modulates ovarian cancer malignancy by regulating P4HA2 expression through binding with miR-30c-5p. These findings elucidate the role of the LINC00240/miR-30c-5p/P4HA2 axis in ovarian cancer and suggest new avenues for targeted therapeutic interventions.

Ulcerative colitis (UC) patients carry a 2.5-fold increased risk of colorectal cancer (CRC), yet the shared multi-scale genetic architecture remains poorly understood. We constructed an integrative framework across tissue, cellular, and variant levels to systematically dissect the pathogenic evolution of this comorbidity across spatiotemporal dimensions.

We integrated GWAS data from 100,204 CRC cases and 12,160 UC patients with tissue-specific MAGMA enrichment, embryonic spatial mapping (gsMap), and multidimensional single-cell prioritization (ECLIPSER, CELLECT, scDRS). We further resolved cell-specific co-expression patterns using hdWGCNA and identified high-confidence causal variants and genes through Bayesian fine-mapping (eCAVIAR, fastenloc) and Open4Gene analysis.

Genetic susceptibility for both diseases was significantly enriched in the terminal ileum and transverse colon, anchored to E16.5 embryonic gut programs. CD4 + T cells emerged as the core immune hub in UC, exhibiting profound immunometabolic polarization (Th17/IL-17 axis and Warburg effect), while progenitors were identified as the primary cellular origin for CRC malignancy. Pathological progression was characterized by a transition from chronic inflammatory stress toward p53-mediated genomic instability, epithelial-mesenchymal transition (EMT), and vascular remodeling. We prioritized Tier 1 candidate genes-ARPC5, PTGER4, CIB1, PREX1, and S100A10-as key mediators of the comorbidity association between inflammation and cancer.

These findings partially support a "genetic programming-microenvironment triggering" hypothesis, where regional vulnerabilities established by embryonic developmental programs are activated by postnatal insults, though its broad applicability warrants caution. This study provides a comprehensive multi-scale molecular framework for understanding UC-CRC comorbidity, offering potential targets for risk stratification and therapeutic intervention.

Asthma is a common chronic respiratory disease in children, often leading to acute exacerbations marked by dyspnea, cough, and wheezing, which frequently necessitate emergency medical care. While standard therapies are effective, the exploration of novel drug delivery routes continues. Oral montelukast is a recognized treatment, but the efficacy of its intranasal formulation for acute attacks remains underexplored. This study aimed to evaluate the clinical effectiveness of intranasal montelukast as an adjunct therapy for pediatric asthma exacerbations. A single-blinded, placebo-controlled, single-center trial was conducted involving children aged 2-12 years hospitalized with moderate to severe acute asthma. Participants were randomized to receive either intranasal montelukast or a placebo alongside standard care. Key outcomes, including the Pulmonary Index Score (PIS), respiratory rate, oxygen saturation, and length of hospital stay, were systematically assessed. The analysis of 25 patients in each group revealed no significant baseline differences. The intranasal montelukast group demonstrated a statistically significant and sustained reduction in PIS scores at critical intervals (8, 12, and 24 hours) compared to the placebo group. Improvements in respiratory rate and oxygen saturation were also more pronounced with the active treatment. Notably, the mean hospital stay was significantly shorter for the montelukast group (2.16 days) than the placebo group (3.12 days). In conclusion, intranasal montelukast shows significant promise as an effective adjunct therapy for acute pediatric asthma, correlating with accelerated clinical improvement and a reduced duration of hospitalization. These encouraging results justify further investigation through larger, multicenter trials to definitively establish its efficacy and safety profile.

This study aimed to examine the extent to which residential ambient air pollution across Australia, globally a relatively low-pollution setting, is associated with cardiovascular and respiratory hospitalisations.

A national, cross-sectional, ecological study.

This whole-of-population study used national air pollution estimates from 2016 and administrative hospitalisation data aggregated across 1155 public health areas from 2016 to 2017, representing 23,236,046 of the Australian population. Population-weighted median concentrations from 2016 of particulate matter ≤2.5 µm (PM2.5; 6.4 µg/m3) and nitrogen dioxide (NO2; 4.4 ppb) were estimated using validated satellite-based land use regression models. Cardiorespiratory hospitalisations (June 2016 to June 2017) were sourced from national administrative data from all hospitals for each public health area. Incidence rate ratios for hospitalisations were estimated for an interquartile range increase in each air pollutant using mixed regression models (age-standardised, adjusted for obesity, smoking, rural/urban and disadvantage) stratified by sex. The population-attributable fraction for each pollutant was estimated across ideal exposure scenarios (5th, 10th and 25th percentile of each pollutant) at each public health area.

PM2.5 and NO2 exposure were consistently associated with greater hospital admissions for cardiovascular and respiratory diseases across both males and females, with estimated incidence rate ratios ranging from 1.02 to 1.06. Across both pollutants, estimated population attributable fractions ranged from 0.9 to 3.9% for cardiovascular diseases, and 1.8 to 7.5% for respiratory diseases.

Despite Australian air pollution levels being relatively low compared with other countries, we observed consistent associations with cardiorespiratory hospitalisations. Given the mounting evidence that air pollution negatively impacts cardiorespiratory health, policies should continuously target air pollution reduction.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder causing chronic oto-sino-pulmonary disease from birth. Since diagnosis is often delayed into childhood or adulthood, early-life disease burdens remain poorly described.

This retrospective study analyzed disease burdens until 2 years of age and outcomes at 6-7 years of age in children diagnosed with PCD near birth at two Canadian PCD centers.

Thirty-five infants (median diagnostic age 34 days) were included. All received daily chest physiotherapy, while 52% received daily inhaled hypertonic saline therapy (IHS) from diagnosis. By 2 years of age, 66% experienced outpatient respiratory exacerbations, 29% had inpatient respiratory exacerbations, 60% required emergency room visits for respiratory illness, and 14% had Pseudomonas aeruginosa in sputum cultures. Abnormal audiology occurred in 91% screened, and 49% required tympanostomy tubes. Despite early diagnosis and therapy, spirometry showed a trend towards obstruction (mean FEV₁/FVC ratio Z-score -1.43) by 7 years of age. Infants on daily IHS from birth (n = 18, mostly at one center) had significantly fewer Pseudomonas aeruginosa sputum isolates (0% vs. 29%, p = 0.02) but significantly increased inpatient respiratory exacerbations (44% vs. 12%, p = 0.04) compared to infants not on regular IHS (n = 17).

Despite early diagnosis, ongoing respiratory surveillance, and regular airway clearance, infants with PCD develop frequent respiratory infections and have high clinical care burdens. Infants have markedly increased risk of hearing loss, warranting universal screening and close follow-up. Inhaled hypertonic saline may influence early Pseudomonas acquisition and hospitalization risk, warranting prospective study of this commonly prescribed therapy.

Bronchiectasis is a chronic lung disease characterized by cough and purulent sputum, recurrent infections, and airway damage. It affects people of all ages and is associated with considerable morbidity and mortality.

A case-control study was conducted to assess factors associated with bronchiectasis. Each patient with HRCT-confirmed bronchiectasis who visited the chest clinic was selected as a case, whereas age- and sex-matched patients without bronchiectasis were selected as controls. Data was collected using a chart review and questionnaire from April 1, 2022, to June 30, 2022. Then, data was entered and analyzed using SPSS Version 25. Frequencies and cross-tabulations were used to summarize descriptive statistics of the data. Chi-square tests and logistic regression were done to establish associations for variables.

The study included 77 cases and 153 controls, with 49.35% of the cases and 33.99% of the controls being between the ages of 41 and 60. After adjusting for potential confounders, a multivariable logistic regression analysis showed that four variables were independent predictors of bronchiectasis. Bronchiectasis was six times more likely to occur in patients with a history of pulmonary tuberculosis (AOR = 6.182; 95% CI (3.16-12.10), p < 0.001). COPD (AOR = 2.896; 95% CI = 1.460-5.746, p = 0.002), bronchial asthma (AOR = 2.124; 95% CI = 1.086-4.154, p = 0.028), and COVID-19 (AOR = 2.786; 95% CI = 1.454-5.340, p = 0.002) also increased the risk of bronchiectasis by more than twofold. There was no significant association between bronchiectasis and age, sex, or smoking history.

Pulmonary tuberculosis, COVID-19, chronic obstructive pulmonary disease, and bronchial asthma are associated with the development of bronchiectasis. Attention should be given to early identification of bronchiectasis among patients with these lung diseases.