Search Results (21,481)

Introduction: Gastric cancer is a prevalent and aggressive malignancy driven by complex signaling networks. Estrogen receptor-α36 (ER-α36), a membrane-localized receptor, mediates non-genomic signaling and promotes tumor progression. ER-α36 can interact with epidermal growth factor receptor (EGFR) to activate downstream mitogen-activated protein kinase (MAPK) signaling, but the detailed mechanism in gastric cancer remains unclear. This study aimed to explore whether ER-α36 promotes gastric cancer progression by regulating serum and glucocorticoid-regulated kinase 1 (SGK1)-mediated Erk1/2 activation. Methods: We collected 53 human gastric adenocarcinoma specimens and detected ER-α36 expression by immunohistochemistry. Bioinformatics analysis was used to identify ER-α36-related kinases. Gastric cancer cell lines (SGC7901, HGC27, NCI-N87, and MFC) were used for in vitro studies. Western blotting, qRT-PCR, immunofluorescence, co-immunoprecipitation (Co-IP), wound healing, MTT, and Transwell invasion analyses, and nude mouse orthotopic tumor models were applied to investigate the function and mechanism of the ER-α36/SGK1/Erk1/2 axis. Results: ER-α36 was positively expressed in 62.3% of gastric adenocarcinoma tissues and was associated with poor differentiation and prognosis. SGK1 was identified as a key kinase downstream of ER-α36. ER-α36, SGK1, and p-Erk1/2 were co-upregulated in gastric cancer tissues and cells. ER-α36 regulated Raf/MEK1/2/Erk1/2 phosphorylation in an SGK1-dependent manner. EGF-induced Erk1/2 activation required both ER-α36 and SGK1. Overexpression of ER-α36 promoted the proliferation, migration, and invasion of gastric cancer cells, while SGK1 knockdown abolished these oncogenic effects. In vivo experiments confirmed that ER-α36 promoted gastric tumor growth and EGFR/Erk signaling, which was attenuated by SGK1 knockdown. Conclusions: ER-α36 contributes to the malignant progression of gastric adenocarcinoma by activating the Erk1/2 pathway through SGK1. The ER-α36–SGK1–Erk1/2 axis may serve as a novel therapeutic target for gastric cancer. Full article

Monitoring dissolved carbon dioxide (CO₂) in aquatic and sediment systems is critical for understanding carbon cycling and climate feedback. This study develops and characterizes a compact, low-cost microbolometer-based attenuated total reflectance (ATR) mid-infrared sensor for direct dissolved CO₂ measurement in liquid and soil-water environments. The system integrates a ZnSe ATR crystal with custom suspended SiN membrane microbolometers and uses evanescent-wave absorption at 4.26 μm with a broadband LED source and computational spectral reconstruction, eliminating the need for an interferometer. Calibration shows excellent linearity (R² ≈ 0.99) over 50–1000 ppm CO₂, with a practical limit of detection (LOD) of ~26–35 ppm at 5–25 °C. UV-induced CO₂ generation from soil-water mixtures was investigated across UV wavelengths, revealing UV-C (254 nm) as optimal, producing net ΔCO₂ ≈ 339 ppm above ambient levels in 30 min. Environmental factors (temperature 5–35 °C, pH 5–11, pressure 1–1.5 ATM, dissolved organic carbon) were systematically evaluated, confirming robust sensor performance (accuracy >90%, correlation r > 0.98 with reference instrument). This sensor represents the first integration of MEMS microbolometer detectors with ATR evanescent-wave spectroscopy for liquid-phase dissolved CO₂, enabling real-time monitoring and rapid sediment organic carbon assessment in a field-deployable platform. Full article

Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with a poor prognosis. While sorafenib serves as the first-line therapy for advanced HCC, its efficacy is frequently hampered by side effects and the development of drug resistance, necessitating the development of novel agents to enhance HCC sensitivity to sorafenib. In this study, we demonstrate that the antihistamine astemizole significantly enhanced the antitumor efficacy of sorafenib in HCC cell lines. This combination treatment cooperatively inhibited HCC cells’ proliferation and induced cell cycle arrest at the G1 phase, as evidenced by decreased cyclin D1 and p-Rb levels and increased p27 expression. Furthermore, the combination of astemizole and sorafenib synergistically inhibited HCC cells’ migration, invasion, and adhesion. It also reduced F-actin polymerization and the expression of metastasis-regulating proteins, including p-Integrinβ1, FAK, and MMP1. Additionally, the combination treatment suppressed tube formation in HUVECs, accompanied by downregulation of HIF-1α and reduced VEGF secretion. Co-inhibition of Eag1 and the ERK/MAPK signaling pathway may underlie the enhanced anti-HCC effects of sorafenib by astemizole. Collectively, these findings indicate that astemizole significantly enhanced the antitumor activity of sorafenib by inhibiting proliferation, metastasis, and angiogenesis in HCC cells, suggesting its potential as a promising adjuvant to improve sorafenib-based therapy in HCC. Full article

Direct ocean carbon capture (DOC) has emerged as a promising strategy for mitigating atmospheric CO₂ levels and addressing ocean acidification. Unlike direct air carbon capture methods, DOC leverages the ocean’s vast carbon storage capacity, offering a scalable and efficient route for carbon dioxide removal. This systematic comparative review categorizes existing DOC methods into three types: (1) biological carbon capture, which relies on photosynthesis by microalgae and marine microorganisms; (2) electrochemical carbon capture, which utilizes water electrolysis to generate H⁺ and OH⁻ ions for pH-driven CO₂ removal; and (3) physical carbon capture, which employs hollow fiber membranes to directly separate CO₂ from seawater. For each technology, we evaluate efficiency, energy consumption, cost, technology readiness level (TRL), scalability, and major challenges. By integrating recent pilot data and providing a critical assessment, this review offers a roadmap for future research in direct seawater CO₂ capture. The comparative analysis reveals that electrochemical methods achieve the highest efficiency (60–85%) but face membrane fouling and electrode degradation challenges, while biological methods offer low-energy operation but suffer from slow kinetics and high harvesting costs, and membrane-based methods provide high removal rates (up to 94%) but require improved fouling resistance. Full article

Microplastics (MPs) often co-occur with heavy metals (HMs), posing combined stress that inhibits plant growth. While plant growth-promoting bacteria (PGPB) are known to alleviate heavy metal toxicity, their role under MP–HM co-contamination and the differential responses of rhizosphere microbial communities remain unclear. This study evaluated the effects of cadmium (Cd) and lead (Pb), polylactic acid (PLA) MPs, and their combined contamination on spinach growth using pot experiments, and assessed the mitigation potential of two PGPB strains. PGPB inoculation significantly increased plant height and dry weight. High-throughput sequencing revealed that pollution treatments and PGPB altered rhizosphere bacterial and fungal community composition and diversity. Microbial shifts were closely associated with soil chemical properties and plant growth. Notably, bacteria and fungi exhibited distinct response patterns to combined stress and remediation. Functional prediction (PICRUSt2) indicated that microbial communities enhanced metabolic processes and nutrient (N and P) cycling to cope with stress. PGPB inoculation reduced heavy metal toxicity, improved soil nutrient status (P and K), increased microbial diversity, and regulated microbial functions, thereby supporting soil ecological stability. These findings provide insights into rhizosphere microbial mechanisms and support the application of PGPB for remediation of MP–HM co-contaminated soils. Full article

This case-control study investigated the association between polymorphisms in the dedicator of cytokinesis 2 (DOCK2) gene and susceptibility to COVID-19 in a Mexican population. Methods: Genotyping of five single-nucleotide polymorphisms (SNPs) in the DOCK2 gene (rs9307 A/G, rs1045176 G/T, rs1045168 C/T, rs2112703 A/C, and rs2287727 A/C) was performed using TaqMan assays in 248 COVID-19 patients and 288 healthy controls. Results: No significant differences were observed in the allelic or genotypic distributions of rs1045176 G/T and rs2287727 A/C between cases and controls. However, under multiple genetic inheritance models (co-dominant, dominant, recessive, heterozygous, and additive), the rs9307 A, rs1045168 C, and rs2112703 A alleles were significantly associated with a reduced risk of COVID-19 (p < 0.05). Furthermore, sub-analyses stratified by genotype in COVID-19 patients revealed that the rs9307 AA, rs1045168 CC, and rs2112703 AA genotypes correlated with altered plasma concentrations of lactic acid dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and ferritin. Conclusions: The DOCK2 SNPs rs9307 A/G, rs1045168 C/T, and rs2112703 A/C are associated with decreased susceptibility to COVID-19 in this population and influence plasma levels of LDH, ALT, AST, and ferritin, suggesting a potential role in disease pathogenesis and severity. Full article

Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age, characterized by hyperandrogenism, insulin resistance, and ovarian dysfunction. Current therapies are often associated with adverse effects, highlighting the need for safer therapeutic alternatives. Peganum harmala (P. harmala), a medicinal plant rich in bioactive metabolites, was investigated through in silico approaches to identify compounds with predicted binding affinity for the androgen receptor (AR), steroid 17α-hydroxylase/17,20-lyase (CYP17A1), and glycogen synthase kinase-3 beta (GSK-3β). GC-MS analysis of P. harmala leaf essential oil collected in Riyadh, Saudi Arabia, identified 109 compounds, with terpenoids as the dominant class (21.89%). The major constituents were cis-chrysanthenyl acetate (3.48%), cis-β-damascenone (3.06%), farnesylacetone (1.44%), β-calacorene (1.36%), dihydroedulan II (1.04%), and trans-calamenene (0.46%). In silico ADMET evaluation indicated that most compounds complied with Lipinski’s rule of five and showed favorable predicted pharmacokinetic properties. Safety profiling suggested an overall acceptable toxicity profile, with minimal predicted CYP450 inhibition, except for L11, which showed broader inhibitory potential. Molecular docking showed that L15 (trans-calamenene), L14 (dihydroedulan II), L6 (β-calacorene), L3 (farnesylacetone), and L8 exhibited higher predicted binding affinity toward the androgen receptor; L3, L10 (cis-β-damascenone), and L16 (cis-chrysanthenyl acetate) interacted with CYP17A1, while L3, L9, and L6 exhibited higher affinity toward GSK-3β. Overall, these findings provide hypothesis-generating in silico predictions of ligand–target binding affinities and drug-likeness profiles. These computational findings highlight the importance of future experimental investigations to substantiate the biological activity, pharmacokinetic behavior, and safety profile of P. harmala constituents. Full article

This study aimed to investigate the molecular mechanisms underlying dopaminergic injury induced by gestational and lactational atrazine (ATR) exposure in rat offspring, with a particular focus on non-coding RNA-mediated regulation. Pregnant rats were exposed to ATR during gestation and lactation. Offspring underwent behavioral testing at postnatal day 21 (PND21) and were sacrificed for midbrain tissue collection at PND28. Behavioral alterations, histopathological changes in the substantia nigra, and dopaminergic marker expression were assessed to evaluate ATR-induced neurotoxicity. Whole-transcriptome sequencing was then performed to identify differentially expressed mRNAs, miRNAs, and lncRNAs, followed by co-expression, protein–protein interaction, and competing endogenous RNA (ceRNA) network analyses. Key targets were validated by qRT-PCR. Candidate molecules identified from transcriptomic and ceRNA analyses were further examined in an ATR-induced neurotoxicity model established in RA-differentiated SK-N-SH cells. Dual-luciferase reporter, Ago2-RNA immunoprecipitation, and biotin-labeled RNA pull-down assays were used to examine putative binding relationships and molecular interactions. In addition, lentivirus-mediated Elavl4 overexpression was performed to further evaluate the role of this candidate regulator in ATR-induced Nurr1 downregulation. Gestational and lactational ATR exposure induced significant behavioral abnormalities in rat offspring. These changes were accompanied by histopathological alterations in the substantia nigra, including reduced TH immunoreactivity, as well as abnormal expression of dopaminergic markers, characterized by decreased TH and Nurr1 levels and increased α-syn expression. Together, these findings indicate the presence of dopaminergic injury. Whole-transcriptome analysis further revealed widespread dysregulation of mRNAs, miRNAs, and lncRNAs in ATR-exposed offspring. Subsequent integrative analysis suggested a potential ceRNA regulatory relationship among Elavl4, miR-301a-5p, and Nurr1, which was further supported by qRT-PCR. Dual-luciferase reporter, RIP, and RNA pull-down assays supported direct interactions between miR-301a-5p and both Elavl4 and Nurr1, as well as their association with the Ago2-containing silencing complex. Moreover, Elavl4 overexpression partially reversed ATR-induced Nurr1 downregulation in vitro. Gestational and lactational ATR exposure induced behavioral abnormalities and dopaminergic injury in rat offspring. Whole-transcriptome analysis combined with experimental validation suggests a potential association between the Elavl4/miR-301a-5p/Nurr1 ceRNA axis and ATR-induced dopaminergic injury, providing insight into the post-transcriptional mechanisms underlying developmental neurotoxicity. Full article

The transformation of university libraries into learning commons has highlighted the importance of informal learning spaces (ILSs). However, the mechanisms through which spatial elements influence learning experiences remain underexplored, particularly in western China. Drawing on person-environment fit theory and a multi-coupling framework, this study develops a four-dimensional analytical model comprising spatial layout, facility configuration, environmental quality, and cultural perception. A mixed-methods approach was employed, including 532 valid questionnaires, behavioral observations, and comprehensive environmental measurements (illuminance, noise, CO₂, PM2.5, TVOC, thermal conditions) across three university libraries in Lanzhou, China. Structural equation modeling (SEM) and coupling coordination degree modeling were used for analysis. Spatial layout (β = 0.324, p < 0.001), facility configuration (β = 0.287, p < 0.001), environmental quality (β = 0.196, p < 0.01), and cultural perception (β = 0.158, p < 0.05) all significantly predicted learning satisfaction, jointly explaining 67.3% of the variance. Learning satisfaction partially mediated the relationship between spatial elements and learning outcomes (indirect effect 31.2%). Coupling coordination degrees ranged from 0.578 to 0.634, revealing a “high coupling, low coordination” pattern, with cultural perception as the common shortfall. Environmental measurements showed CO₂ concentrations ranging from 823 to 946 ppm in quiet zones and up to 1085 ppm in lounge areas, correlating negatively with satisfaction (r = –0.41, p < 0.05). Spatial elements influence learning outcomes primarily through satisfaction enhancement. An integrated optimization framework is proposed, offering actionable strategies for ILS design in similar contexts. Full article

Background/Objectives: Excess consumption of energy-dense foods (EDF; ultra-processed snacks, sweets, and sugar-sweetened beverages) among preschool-aged children is a public health concern, particularly in low-income families. Caregiver parenting style, psychological stress, and food-parenting practices (FPP) may shape children’s EDF consumption, yet little is known about how these factors operate in real time. This exploratory pilot study examined (1) associations between baseline characteristics and EDF feeding episodes across 1 week and (2) whether caregivers’ momentary stress during EDF episodes related to FPP used. Methods: In total, 22 caregivers of Head Start children (ages 3–5) completed baseline measures and 7 days of ecological momentary assessment (up to seven prompts/day). At each prompt, caregivers reported child EDF consumption in the past hour; if confirmed, they reported FPP used and rated momentary stress. Aim 1 used Poisson regression to model caregiver-level EDF episode counts. Aim 2 tested momentary stress–practice associations during EDF episodes using GEE, with within-person and between-person stress modeled separately. Results: Authoritarian parenting was associated with a higher weekly rate of EDF episodes (RR = 1.43, 95% CI 1.23–1.66, p < 0.001); authoritative parenting trended lower (RR = 0.90, p = 0.065). Higher baseline stress was associated with more EDF episodes (RR = 1.25, p = 0.001). Momentarily, elevated stress above a caregiver’s own average increased odds of using food as a reward (OR = 1.08 per +10 points, p = 0.011), while higher average momentary stress was associated with co-eating (OR = 1.59, p = 0.042). Domain-level FPP composites showed no association with momentary stress. Conclusions: Authoritarian parenting and higher caregiver stress were associated with increased EDF feeding, and momentary stress was linked to reward-based feeding during those episodes. These hypothesis-generating findings suggest potential behavioral targets for just-in-time adaptive intervention, pending replication in adequately powered studies. Full article

Nosema ceranae is a common and highly contagious fungal pathogen that primarily infects the gut of adult honeybees, causing nosemosis. As a chronic disease of the digestive system, it poses a global threat to honeybee health and colony sustainability. This study aimed to investigate the inhibitory effects of different concentrations of Scutellaria baicalensis aqueous extract on N. ceranae in the intestines of infected Apis cerana through feeding experiments. In addition, the therapeutic efficacy of its major active component, baicalin, was evaluated, and its potential molecular mechanisms of action were explored. The results showed that, compared with the control group, administration of S. baicalensis aqueous extract at concentrations of 1 mg/mL, 5 mg/mL, and 10 mg/mL significantly reduced midgut spore loads (p < 0.05). Further experiments showed that a 0.5 mg/mL baicalin sucrose solution, prepared with 0.5% (v/v) DMSO as co-solvent, exhibited optimal solubility and significantly inhibited the proliferation of spores in the honeybee midgut. Transcriptomic analysis of A. cerana revealed varying numbers of significantly differentially expressed genes among the baicalin-treated (HG) group, the co-solvent control (DMSO) group, and the blank control (C) group. Four candidate DEGs associated with the effects of baicalin were further identified, namely LOC108003965, LOC108000905, LOC107996681, and CYP4G11. Gene Ontology enrichment analysis showed that, in the comparison between the HG group and the C group, these DEGs were significantly enriched in six functional categories: iron ion binding, phosphoric ester hydrolase activity, heme binding, tetrapyrrole binding, hydrolase activity (acting on ester bonds), and oxidoreductase activity (acting on paired donors, with incorporation or reduction of molecular oxygen). Collectively, these results demonstrate that S. baicalensis aqueous extract effectively inhibits the proliferation of N. ceranae within the host, and its active component, baicalin, exhibits a similar inhibitory effect. The present study proposes a novel strategy in which baicalin may enhance host endogenous chitinase-related activity to target and disrupt the spore wall, offering a new perspective for the prevention and control of honeybee nosemosis. Full article

Fusobacterium nucleatum (F. nucleatum), a key oral pathogen, promotes colorectal cancer (CRC) progression via gut translocation. Although gut probiotics provide colonization resistance against pathogens, antibiotic-induced dysbiosis may facilitate F. nucleatum integration and increase the risk of CRC. The mechanisms underlying probiotic–F. nucleatum antagonism and antibiotic modulation remain unclear. A 33-strain probiotic consortium and F. nucleatum subsp. Polymorphum (F. polymorphum) ATCC 10953 were co-cultured. The inhibitory effects of probiotics on F. nucleatum and the impacts of antibiotics (ABXs) on the microbial community structure in the co-culture system and on the probiotic-mediated inhibition of F. nucleatum were evaluated using spent medium assays, plate confrontation tests, growth curves, qRT-PCR, metagenomic sequencing, and transcriptomics. Hydrogen peroxide/pH/lysine assays and coaggregation models were performed to probe the associated mechanisms. Probiotics strongly inhibited the growth of F. nucleatum in a dose-dependent manner, primarily via organic acids, while F. nucleatum enriched amino acid/vitamin biosynthesis pathways without major growth suppression. Antibiotics weakened probiotic antagonism, shifted species abundance (↓ L. plantarum, ↑ L. paracasei), induced adaptive stress responses in F. nucleatum (↑ nucleotide metabolism, propanediol degradation, pdxS), and reduced lysine biosynthesis. Lysine supplementation restored probiotic abundance and disrupted F. nucleatum coaggregation. Multi-strain probiotics exert potent colonization resistance effects against F. nucleatum, mainly through organic acids and metabolic interference. Antibiotic-induced dysbiosis impairs this protective effect and may promote the persistence of F. nucleatum, which has been implicated in CRC risk. Targeted probiotic strategies may offer novel preventive approaches. Full article

Background: Health-related behaviors often cluster during young adulthood, potentially increasing the risk of long-term adverse health outcomes. Understanding how lifestyle risk behaviors co-occur among university students is essential for developing targeted health promotion strategies. Objective: This study aimed to identify lifestyle risk profiles among university students based on the co-occurrence of smoking behavior, alcohol consumption, sedentary behavior, and body weight status. Methods: A cross-sectional study was conducted with 147 university students enrolled in a physical education and sport undergraduate program (mean age: 20.58 ± 2.94 years; 80.3% male). Physical activity and sedentary behavior were assessed using the International Physical Activity Questionnaire–Short Form (IPAQ-SF), while smoking and alcohol consumption were self-reported. Body mass index was used to classify weight status. Lifestyle risk profiles were identified using two-step cluster analysis based on regular smoking, alcohol consumption, sedentary behavior, and overweight/obesity. Differences in cluster distribution according to sex and federated athlete status were examined using chi-square tests. A two-step cluster analysis based on the Bayesian Information Criterion (BIC) and silhouette measure was used to identify lifestyle risk profiles. Results: Overall, 46.9% of participants had experimented with tobacco, 11.6% were current smokers, and 74.8% reported alcohol consumption. Participants accumulated an average of 3772.25 ± 1957.99 MET-min/week of physical activity. Three distinct lifestyle risk profiles were identified. Cluster 1 (46.9%), labeled the alcohol profile, was characterized by alcohol consumption without smoking and no prevalence of being overweight. Cluster 2 (20.4%), the multiple-risk profile, included participants who reported regular smoking, with nearly half presenting sedentary behavior and overweight/obesity. Cluster 3 (32.7%), the overweight profile, was characterized by overweight/obesity combined with alcohol consumption but no smoking. No significant differences were observed in the distribution of lifestyle profiles according to sex (p = 0.111) or federated athlete status (p = 0.087). Conclusions: Lifestyle risk behaviors cluster into distinct profiles among university students, with alcohol consumption appearing across multiple profiles and smoking concentrated in a specific high-risk group. These findings highlight the need for targeted health promotion strategies addressing multiple co-occurring behaviors within university populations. Full article

The chemical equilibria of metal ions between soil solution and solid phases govern the solubility of metals in soil. However, the identity of these controlling phases remains poorly understood in historically polluted environments. This study aimed to identify the dominant mineral phases regulating the activities of Zn²⁺, Cd²⁺, Pb²⁺, and Ni²⁺ in soils subjected to long-term contamination from sewage sludge, municipal solid waste, river water, and industrial effluents across India. The soil samples were collected from various locations historically polluted by sewage sludge, municipal solid waste, polluted river water and industrial effluents. The free ion activities of Zn²⁺ (pZn²⁺), Cd²⁺ (pCd²⁺), Pb²⁺ (pPb²⁺) and Ni²⁺ (pNi²⁺) in soil pore water were estimated using the geochemical speciation model WHAM-VII. The metal ion activities were higher in industrial effluents and solid waste-treated soils as compared to other contaminated soils. The solubility of Zn and Cd in soils contaminated with Zn-smelter effluents was controlled by franklinite (ZnFe₂O₄) in equilibrium with goethite (α-FeOOH) and otavite (CdCO₃), respectively. Identification of minerals further reveals that nickel ferrite (NiFe₂O₄) in equilibrium with lepidocrocite (γ-FeOOH) governs the activity of Ni²⁺ in cycle factory effluent-irrigated soils of Sonepat, Haryana. At the municipal solid waste-contaminated site, the Pb²⁺ activity was controlled by exchangeable Pb in soils, whereas Zn²⁺ activity was governed by willemite (Zn₂SiO₄) in equilibrium with quartz (SiO₂). These findings provide new insights into mineralogical controls on heavy metal solubility under diverse contamination scenarios. Formation of highly soluble minerals like otavite, willemite, and nickel ferrite suggested the potential ecological risk of Cd, Zn, and Ni, respectively, in polluted soils. Full article

Human parainfluenza virus type 4 (hPIV4) remains poorly characterized compared with other hPIV serotypes and information on its genomic diversity is particularly limited for Russia and Eastern Europe. In this study, we report the first complete genome sequences of hPIV4 isolates from Russia and place them in the context of global hPIV4 genetic diversity. Eight hPIV4 viruses were isolated in cell culture from respiratory samples collected from hospitalized children in Saint Petersburg between 2017/2018 and 2023/2024. Complete viral genomes were recovered using a metagenomic whole-genome amplification approach based on SMART-9N technology. Phylogenetic analysis of 178 complete hPIV4 genomes showed clear separation into hPIV4a (n = 132) and hPIV4b (n = 46) subtypes. Based on genetic distance approach, hPIV4a formed two major clusters, with the dominant cluster B subdivided into four subclusters (B1–B4); and subcluster B4 further resolved into four genetic lineages. All Russian isolates belonged to the subcluster B4 and were distributed among multiple co-circulating lineages. In contrast, hPIV4b genomes segregated into three distinct clusters, reflecting structured genetic diversity within the subtype. Collectively, this study provides, to the best of our knowledge, the first p-distance-based framework for hPIV4 whole-genome classification and contributes new complete genome sequences for an underrepresented region. Full article