Triple-negative breast cancer (TNBC) lacks effective targeted therapies, and the mechanisms by which developmental endothelial locus-1 (EDIL3/Del-1) promotes TNBC remain incompletely defined. We profiled Del-1 and AMPK subunits in TNBC cell lines by RT-PCR and immunoblotting, performed functional assays in CRISPR/Cas9 Del-1 knockout and AMPKβ-manipulated cells, and evaluated AMPKβ in early-stage TNBC tumors using tissue microarrays (TMA) (immunohistochemistry; n = 100) and AMPKβ2 mRNA quantification. Del-1 and AMPKβ were enriched in TNBC cells, most prominently in the mesenchymal stem-like subtype, whereas AMPKα levels were relatively stable. Increased Del-1 and activated AMPKβ enhanced proliferation and invasion, while Del-1 deletion reduced AMPKβ expression and suppressed tumor-promoting phenotypes. Mechanistically, Del-1 increased AMPKβ phosphorylation at serine 108, and a phospho-mimetic AMPKβ mutant further amplified oncogenic effects. In the pilot TMA study, high AMPKβ protein expression showed a trend toward poorer DFS in Kaplan-Meier analysis, while multivariate analysis identified high AMPKβ protein expression as an independent factor associated with poorer DFS in patients with early TNBC. These data support AMPKβ as a key mediator of Del-1-driven signaling and suggest AMPKβ could be a therapeutic target in aggressive TNBC subsets.

In glioblastoma, the strong immunosuppression of the tumor immune microenvironment fosters tumor aggressiveness and decreases the effectiveness of therapeutic interventions, including immunotherapies. An intricate network of connections among tumor cells, stroma and infiltrating immune cells sustains immunosuppression. Lectins are immunoregulatory glycan-binding receptors contributing to immunosuppression. Their targeting is proposed as an appealing strategy for anti-cancer therapy. In this work, network-based approaches were exploited to identify a lectin profile that could dissect the complexity of tumor-immunity interactions in glioblastoma. Differential co-expression analysis, employing TCGA, CGGA and GTEx databases (145, 133 and 255 samples, respectively), identified a cluster of novel C-type lectins, with ASGR2 and CLEC12A as principal hubs. Furthermore, TIMER2.0 analysis revealed that their expression was significantly associated with immunosuppressive cells. ASGR2 and CLEC12A expression was also validated by cytofluorimetric analysis on both tumor and liquid biopsies from 20 glioblastoma patients. We report that ASGR2 and CLEC12A C-type lectins are associated with tumor-infiltrating immunosuppressive myeloid subsets and discriminate patients' poor prognosis. These results suggest that C-type lectins may contribute to the immunosuppressive network sustained by infiltrating myeloid immune cells in GB, resulting in exploitable targets for therapeutic interventions.

Deuterium abundance has been proposed as a modulator of cellular metabolism; however, its influence on cancer-associated gene expression networks remains incompletely characterized. We analyzed A549 lung adenocarcinoma cells cultured across four deuterium concentrations (40, 80, 150, and 300 ppm) using NanoString nCounter profiling. Expression data were processed through multistep filtering, symbolic trajectory encoding, and density-based spatial clustering (DBSCAN) to identify extreme expression responders, and Gaussian mixture modeling (GMM-6) to resolve coordinated gene-expression modules. DBSCAN identified 11 outlier genes under deuterium depletion, including reduced expression of multidrug-resistance-associated ABCB1 (-42% at 80 ppm), proliferative signaling component FGFR4 (-19%), and transcriptional amplifier MYCN (-24%). In contrast, enrichment at 300 ppm produced a broad increase in oncogenic expression (mean +44%), with marked elevation of inflammation-related (IL6, TGFBR2) and invasion-associated (MMP9) genes. GMM-6 clustering of the remaining core network resolved six functional modules, indicating that depletion preferentially reduces expression of genes associated with plasticity-related programs (Cluster 5: TGFB1, S100A4), while basal survival-associated genes (Cluster 6: BIRC5, RET) remain comparatively stable. Together, these results indicate that deuterium concentration acts as a bidirectional modulator of gene expression programs in the A549 model, with enrichment broadly elevating oncogenic expression and moderate depletion associated with selective downregulation of genes linked to resistance, signaling, and invasive behavior. Significance: Deuterium depletion is associated with reduced expression of genes involved in multidrug resistance, growth-factor signaling, and transcriptional amplification, revealing deuterium-responsive transcriptional vulnerabilities within the A549 lung adenocarcinoma model.

PAX3 plays a vital role in regulating proper growth, migration, differentiation, and survival during development of normal tissues, including those derived from the embryonic neural crest. PAX3 is a transcription factor with two separate DNA-binding domains and can positively (and less frequently, negatively) regulate gene expression. The levels of PAX3 can be modified by upstream molecular pathways, and its subsequent downstream functions are regulated through a wide range of protein interactions and posttranscriptional modifications. PAX3 direct downstream target genes are other transcription regulators and factors that modulate cellular proliferation, lineage specificity, migration, and survival. The pathways that PAX3 regulates during development may be recycled and subverted during disease progression, for example, during cancer progression, growth, and metastasis. Indeed, PAX3 is overexpressed in several cancers, including melanoma, neuroblastoma, and rhabdomyosarcoma. While there is still much that is unknown about the mechanisms by which PAX3 controls such a wide array of key cellular functions, a great deal of progress has been made to advance our understanding of this critical and multi-faceted factor.

Xeroderma pigmentosum group B (XPB/ERCC3) and group D (XPD/ERCC2) helicases are integral components of the transcription factor IIH (TFIIH) complex, coordinating DNA unwinding during transcription initiation and nucleotide excision repair (NER). XPB functions as an ATP-driven translocase that generates torsional strain to promote promoter melting and DNA opening at lesion sites, whereas XPD acts as a 5' to 3' helicase responsible for lesion verification and extension of the repair bubble. Structural and biochemical studies have clarified how TFIIH subunits regulate these helicases-p52 and p8 modulate XPB's translocation activity, while p44, p62, and MAT1 control XPD's helicase function through conformational and compositional transitions within the complex. Beyond their canonical roles, XPB and XPD participate in diverse cellular pathways, including cell-cycle regulation and oxidative stress response, highlighting their involvement in maintaining genome integrity beyond repair and transcription. Mutations in either helicase lead to xeroderma pigmentosum (XP), trichothiodystrophy (TTD), or combined XP/Cockayne syndrome (XP/CS) phenotypes, emphasizing the essential role of TFIIH integrity for human health. Recent biochemical and pharmacological advances have further revealed the therapeutic relevance of these helicases-XPB as a target of small-molecule inhibitors such as triptolide, Minnelide, and spironolactone, and XPD as a potential modulator of cancer sensitivity to DNA-damaging treatments. Collectively, XPB and XPD exemplify the structural and functional versatility of TFIIH helicases across repair, transcription, and genome maintenance.

Molecular subtypes are potential prognostic and predictive tools in muscle-invasive bladder cancer (MIBC). However, subtype concordance between primary tumors and metastases, as well as subtype-specific differences in metastatic patterns, remain poorly characterized. The present study aimed to evaluate the concordance of molecular subtypes between primary tumors and matched lymph node (LN) metastases and to explore their association with metastatic patterns. Gene expression-based molecular subtypes were determined according to the five-tiered Lund Taxonomy in 182 primary tumor samples and 34 matched LN metastases from patients with MIBC who underwent upfront radical cystectomy. Subtypes identified in the primary tumors were compared with those in matched positive LNs and patterns of distant metastasis were analyzed. In addition, the association between molecular and histological subtypes was also investigated. We found an overall 62% subtype concordance between primary tumors and corresponding LN metastases, with complete concordance in the basal/squamous subtype, lower concordance in the luminal subtypes (genomically unstable: 67%; urothelial-like: 57%), and low concordance (33%) in the mesenchymal-like (Mes) subtype. Luminal subtypes were associated with LN-only metastases and less frequent distant metastases. In contrast, the Mes subtype was associated with a higher rate of distant metastases (43%), and more frequent multiorgan involvement (≥3 organs: 40%). Higher expression of the mesenchymal gene CDH2 and the neuronal-differentiation genes GNG4 and ENO2 was associated with a higher number of metastatic sites. Gene expression-based molecular subtypes may change between primary MIBCs and matched LN metastases, and these differences appear to be subtype-dependent. Mes subtype and the expression of CDH2 as well as GNG4 and ENO2 are associated with more frequent and extensive metastases, indicating highly aggressive forms of MIBC.

Hongwu mixture (HWM) consists of Taxus chinensis, Marsdenia tenacissima, Rhizoma Curcumae, and Semen coicis. The objective of this study was to ascertain the potential role of the Hongwu mixture (HWM) in the treatment of triple-negative breast cancer (TNBC). TNBC cells were treated with low, medium, and high doses of HWM, and CCK-8 assays were conducted to evaluate the impact of different doses of HWM on TNBC cell viability. The target molecules of HWM were predicted using RNA-sequencing, and molecular docking models between HWM components and target proteins were developed. As the dose of HWM increased, TNBC cell viability gradually decreased. HWM inhibited the proliferation and mobility of TNBC cells, slowed the tumor growth, and upregulated the apoptosis of TNBC cells. HWM promoted Zinc finger protein 143 (ZNF143)-mediated transcriptional activation of salvador family WW domain-containing protein 1 (SAV1) by stabilizing ZNF143 protein expression, leading to phosphorylation of large tumor suppressor homolog 1 (LATS1) and Yes-associated protein 1 (YAP1). Knockdown of ZNF143/SAV1 signaling impaired the therapeutic effect of HWM, and treatment with verteporfin, pharmacological inhibition of YAP/TAZ, reversed the effects of knockdown of SAV1. Therefore, HWM might offer a potent strategy for managing TNBC effectively.

This study aims to investigate the correlation between blood leukocyte, CRP, LDH, and cytokine levels and the severity of illness in children with adenovirus pneumonia.

A total of 100 children with adenovirus pneumonia (55 mild cases and 45 severe cases) who were treated at Guangzhou Women and Children's Medical Center from January 2022 to January 2024, and 40 healthy children as a control group, were selected. Clinical data, some laboratory test data, and serum cytokine levels detected by flow cytometry were collected, and statistical methods were used to analyze the correlation between relevant indicators and the severity of the illness.

The research showed that among general clinical manifestations, the proportions of children with fever, dyspnea, pleural effusion, and moist rales in the severe group were all higher than those in the mild group (p < 0.05). Among the collected laboratory test data, indicators such as WBC, neutrophils, and LDH were significantly higher than in the mild group and the control group (p < 0.05) and were positively correlated with the severity of the disease. Regarding the tested cytokines, most children with adenovirus pneumonia showed elevated levels, and cytokines such as IL-6, IL-2, and IL-8 were significantly positively correlated with the disease. In the ROC curve analysis, NEU 6.03 × 10⁹/L (sensitivity 82.2%, specificity 72.7%, AUC 0.830) and IL-6 41.823 pg/mL (sensitivity 75.6%, specificity 81.8%, AUC 0.833) demonstrated certain value in the early identification of children with severe disease.

In this study, laboratory indicators (C-reactive protein, lactate dehydrogenase, neutrophils, etc.) and changes in the levels of specific cytokines (TNF-β, IL-2, IL-6, IL-8, etc.) in children with adenovirus pneumonia were closely related to the severity of the disease. Notably, neutrophil count and interleukin-6 were significantly positively correlated with disease severity and had high AUC values, suggesting they may be important parameters for early prediction of the progression of mild adenovirus infection to severe disease.

Respiratory syncytial virus (RSV) is a leading cause of respiratory infections in infants and older adults, with epidemiological patterns shaped by viral evolution and diversity. To investigate the molecular epidemiology of RSV before and after the COVID-19 pandemic, we conducted genomic surveillance and phylodynamic analyses of RSV-A and RSV-B circulating in Maryland from 2018 to 2024. Whole-genome sequencing of RSV-positive samples (n = 451) was performed, and genomes were analyzed with phylogenetic and Bayesian methods to estimate evolutionary rates, population dynamics, selection pressures, and genetic diversity. RSV-A predominated in most seasons, while RSV-B showed episodic surges in 2018 and 2023. All RSV-A genomes belonged to the ON1 genotype, and RSV-B belonged to BA9, with sequential clade dominances including A.D.1, A.D.5.2, A.D.1.6, and B.D.E.1 across different epidemic seasons in Maryland. Bayesian analyses estimated evolutionary rates of 7.07 × 10^-4 substitutions/site/year for RSV-A and 1.02 × 10^-3 substitutions/site/year for RSV-B and temporal fluctuations in effective population size linked to pandemic-related disruptions. RSV-A displayed greater overall entropy, yet RSV-B evolved slightly faster. Genetic variability was concentrated in the G glycoprotein, with positively selected sites at codon 273 (RSV-A) and codon 217 (RSV-B). These findings demonstrate temporal fluctuations in RSV-A and RSV-B predominance, clade replacement, and ongoing viral adaptation throughout the COVID-19 era, underscoring the importance of integrated genomic and phylodynamic studies.

Norovirus is the leading cause of acute gastroenteritis outbreaks worldwide. A total of 1859 norovirus outbreaks were reported from 2016 to 2022 in Beijing, China. GII.2[P16] was the predominant genotype during 2016-2021, and GII.3[P12] during 2021-2022. In the early stage of the COVID-19 epidemic (January to June of 2020), strict prevention and control measures were implemented, and only eight norovirus outbreaks were reported. Most norovirus outbreaks occurred in schools (95.6%, 1778). As the level of schooling rises, the scale of norovirus outbreaks also increases (median case numbers: 8 for kindergarten, 10 for primary school, 11 for secondary school, and 14 for college; p trend < 0.001), while the attack rate decreases (median attack rates were correspondingly 25.8%, 17.5%, 10.0%, and 8.8%; p trend < 0.001). Compared to outbreaks caused by person-to-person transmission, foodborne and waterborne outbreaks are larger in scale. Delayed outbreak response is also a risk factor for larger-scale outbreaks. Norovirus outbreaks have emerged as a significant concern for public health in Beijing. Persistent genotyping efforts are essential to facilitate early warning. Outbreaks in different locations or through different transmission routes require specific prevention and control measures.