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Mechanism of Astragaloside-Brucea javanica oil nanoemulsion against oral squamous cell carcinoma through CDK1/MTFR2: Network pharmacology, bioinformatics, and experimental studies

Objective This study aims to investigate the core target of Astragaloside-Brucea javanica oil nanoemulsion (AS/BJO-NEs) against oral squamous cell carcinoma (OSCC) through network pharmacology, bioinformatics, and in vivo/in vitro experiments, elucidating its effects on epithelial-mesenchymal transition (EMT) mediated via MTFR2 and the underlying molecular mechanisms. Methods By integrating network pharmacology and weighted gene co-expression network analysis, critical gene modules linked to tumor phenotypes, EMT-related adverse prognosis, and elevated MTFR2 expression were identified, pinpointing the core target gene. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment Analysis, molecular docking and molecular dynamics simulation were utilized for analysis and verification. OSCC cells (SCC9 and CAL27) were cultured, and stable cell lines with CDK1 knockdown or overexpression were established. The effects of AS/BJO-NEs on cell proliferation, migration, invasion, as well as the expression levels of related genes and proteins were evaluated. In vivo, OSCC xenograft models were established in nude mice. Following treatment with AS/BJO-NEs, tumor growth inhibition and changes in the expression of relevant genes were assessed. Results CDK1 is the core target gene of AS/BJO-NEs against OSCC, and the two can bind stably. CDK1 and MTFR2 showed highly expressed in OSCC and strongly correlated with poor prognosis and EMT. In vitro experiments revealed that AS/BJO-NEs could suppress the proliferation, migration and invasion of OSCC, and down-regulate CDK1, MTFR2 and N-cadherin, whereas up-regulate E-cadherin expression. Knockdown and overexpression of CDK1 further confirmed its effects on OSCC cell phenotype, its regulatory relationship with MTFR2, and the intervention effects of AS/BJO-NEs. In vivo experiments confirmed that AS/BJO-NEs significantly inhibited tumor growth and reduced the expression of CDK1 and MTFR2 in tumor tissues. Conclusion This study demonstrated that AS/BJO-NEs inhibited the proliferation, migration, invasion and EMT process of OSCC by down-regulating CDK1 and subsequently reducing MTFR2 expression, exerting anti-tumor effects and providing new possibilities and a theoretical foundation for OSCC treatment.

A Multi-factor analysis for evaluating habitat suitability of traditional settlements in Huizhou

Epidemiological and clinical analysis, and outcomes of tuberculosis co-infection among people living with HIV in Türkiye (2014–2024) ClinSurv HIV cohort: A large case series

Background Tuberculosis (TB) is one of the most common opportunistic infections in people living with HIV (PLHIV). Mycobacterium tuberculosis may cause more TB in all stages of HIV infection than in the general population, with the incidence of TB and the spread of pulmonary TB to other organs increasing as the CD4 count decreases. Objective In this HIV cohort study, we aimed to evaluate the clinical features, diagnosis, and prognosis of TB among PLHIV in Türkiye. Materials and methods We conducted a retrospective cohort study to analyze clinical outcomes and identify determinants of mortality among people living with HIV (PLHIV) co-infected with tuberculosis. We included 264 patients diagnosed and treated for TB across six centers in Türkiye. We extracted clinical, demographic, laboratory, microbiological, and radiological data from patient medical records. To identify independent predictors of mortality, we performed multivariable logistic regression and reported the results as odds ratios (ORs) with 95% confidence intervals (CIs). Results Of the 9,687 PLHIV who were followed for 10 years, 2.7% (264 individuals) developed TB. The median age of these individuals was 40 years, and 89% were male. The prevalence of pulmonary TB only, extrapulmonary TB only, and the coexistence of pulmonary and extrapulmonary TB were 42.4%, 48.8%, and 8.7%, respectively. Opportunistic infections and cancers were found in 23% (62 out of 264) of patients with HIV/TB co-infection. Among patients with HIV/TB co-infection, 42% showed lymphadenopathy, with 70% of these cases being generalized. In patients who underwent chest CT scans (n=200), radiological patterns revealed post primary TB in 46%, primary TB in 36%, and miliary TB in 18%. The positivity rates of Ehrlich-Ziehl-Neelsen staining (EZN), polymerase chain reaction (PCR), and TB cultures in clinical samples were found to be 47.5%, 72.5%, and 53%, respectively. Most of our patients (95%) were given the standard TB treatment regimen (HRZE), with a paradoxical reaction observed in 11.6% of cases and hepatotoxicity occurring in 18% of cases. Age, CD4 count (<200 cells/mm3-late presenters), and thrombocytopenia were identified as independent risk factors for mortality in the 58 patients (22%) who died after diagnosis. Conclusion Even today, more than one fifth of patients with HIV–TB co-infection in our cohort died. Mortality was higher among individuals who presented late with tuberculosis disease, especially those with advanced immunosuppression (CD4 <200 cells/μL). These findings underscore the urgent need for early HIV diagnosis and systematic TB screening to reduce co-infection–related mortality and improve clinical outcomes.

Gut microbiota from Mori fructus (Morus alba L.) polyphenols and polysaccharides-dosed mice activates the PPARα/PGC-1α signaling pathway to mitigate HFD-induced metabolic syndrome in mice

Three-dimensional multiple object tracking (3D-MOT) performance in young soccer players: Age-related development and training effectiveness

Objectives The aim of the present study is to examine the developmental trajectory of 3D-MOT performance in young soccer players, and to investigate the age-related 3D-MOT performance training effect. Methods First, Experiment 1 assessed 3D-MOT performance of 404 male soccer players aged 12–18 years. Then, 127 athletes in Experiment 1 aged 13, 15, and 17 were selected as participants in Experiment 2, randomly assigned to intervention group and the control group. The intervention group but not the control group received 15 sessions of 3D-MOT training (3 sessions per day for 20 minutes for 5 days). Subsequently, post-test of 3D-MOT performance was conducted on the two groups. Results Experiment 1 showed that there was a significant main effect of age on the peak speed (p < .001,η² = .041) of 3D-MOT performance, with the performance of participants aged 15 significantly higher than that of those aged 13 (p = .018, d = −0.559). Experiment 2 revealed a significant main effect of the intervention, including peak speed (p < .001), average speed(p < .001),and speed threshold(p < .001), but the interaction between the intervention and the age group was not significant. Conclusions This research provide evidence that the 3D-MOT performance of young soccer players exhibits an increase between 13 and 15. Moreover, the results showed a significant training improvement in youth soccer players, but there was no significant relationship between the age-related development of 3D-MOT and the training effect in young soccer players. The above results provide new insights into soccer science and practice. Given the lack of data for those players younger than 12, this restricts the inference of whether there are potential sensitive periods. The study suggest that in the future, more evidence on athletes under the age of 12 be added to enhance the understanding of the full developmental trajectory of 3D-MOT performance in soccer players.

Lumbar and pelvic CT image segmentation based on cross-scale feature fusion and linear self-attention mechanism

Derivation of a novel multi‐gene prognostic model based on regulated cell death pathways in acute myeloid leukemia: A comprehensive bioinformatic analysis integrating gene expression, mutation profiling, and immune infiltration

Background Acute myeloid leukemia (AML) is a highly aggressive hematologic malignancy with dismal survival outcomes, where dysregulation of regulated cell death (RCD) pathways plays a pivotal role in leukemogenesis and therapeutic resistance. Methods Differential expression analyses were performed comparing AML samples with healthy bone marrow. Diagnostic differentially expressed genes (DEGs) were then intersected with curated gene sets representing apoptosis, pyroptosis, autophagy, necroptosis, and ferroptosis to derive an RCD-based gene signature. Prognostic markers were identified by univariate Cox regression, and these markers were refined using LASSO regression to construct a multi-gene prognostic model that generated an individual risk score (RS) for each patient. The performance of the model was validated internally through Kaplan–Meier survival analyses and receiver operating characteristic (ROC) curves for 1-, 3-, and 5-year survival, and externally confirmed in an independent TARGET-AML cohort. In addition, mutation analysis was conducted using the maftools package, and immune infiltration profiling was performed with CIBERSORT and xCell to characterize the molecular landscape of the risk groups. Results Our integrative approach yielded a four-gene prognostic model incorporating ARHGEF35, GSN, ELANE, and AKT3. High RS was strongly associated with adverse overall survival, with Kaplan–Meier analyses showing p-value < 0.0001 in the training cohort and p-value = 0.0026 in the testing cohort. The model demonstrated robust predictive accuracy with AUC values of 82%, 87%, and 91% for 1-, 3-, and 5-year survival in the training set, and 65%, 81%, and 94% in the testing set. Mutation analysis revealed that DNMT3A and RUNX1 mutations were significantly enriched in high-RS patients (p-value = 0.0015 and p-value = 0.0086, respectively), whereas KIT mutations were more prevalent in low-RS patients (p-value = 0.0058). Immune profiling indicated that high-RS patients had increased M2 macrophage infiltration (p-value = 0.0027) and reduced resting mast cells (p-value = 0.0033). Conclusion These findings establish that an RCD-based multi-gene risk model can robustly stratify AML patients by prognosis and illuminate underlying genomic and immunologic mechanisms, thereby offering promising avenues for personalized therapeutic strategies.

Presence of high-risk nano particulate matters in powder injection: microscopic evaluation and investigation of particles contamination

Public education during epidemics of infectious diseases: A national mixed-method study with parallel convergent design in a low and middle-income country

Introduction Proper and effective public education during epidemics of infectious diseases can have a key effect in controlling epidemics and reducing their complications. Therefore, the present study aims to assess public education methods during infectious disease epidemics from the perspectives of both the public and experts in Iran. Method The present study is a mixed-methods (quantitative-qualitative) with a parallel convergent design conducted in 2024 in Iran. The public’s views on the effectiveness, strengths, and weaknesses of each method used for educating people during epidemics, with a focus on the COVID-19 epidemic, were collected through a self-development valid and reliable questionnaire (with closed and open-ended questions). Quantitative data was analyzed using SPSS:16 software. In the qualitative section, data were collected by semi-structured interviews and manually analyzed using content analysis methods. Results Television (79.9%), social networks (78.8%), and websites (78.5%) were introduced as sources that have performed best, provided various information and education, had a high impact on the audience, and successfully gained people’s trust during epidemics of infectious diseases. In the qualitative section, the majority of participants identified in-person training as the most effective method of educating people. Utilizing the capacities of mass media and providing accurate information to the public were strengths, while dissemination of false and unscientific information and lack of trust in relevant institutions were identified as weaknesses in educating people during epidemics of infectious diseases. Conclusion In this study, an attempt was made to provide comprehensive and sufficient information for decision-making and effective planning for public education in the next epidemics of infectious diseases.

The number of immune defence and counter-defence systems sustained in the arms race between prokaryotes and viruses

Exposure to maternal nicotine in utero and/or via lactation alters craniofacial development in mice

The Center for Disease Control’s National Birth Defects Prevention Study data suggests that maternal nicotine use may increase the incidence of craniofacial birth defects and growth anomalies like craniosynostosis, cleft palate, and/or lip in offspring. Craniofacial growth proceeds by expansion at fibrous sutures and synchondroses. In the cranial base, synchondroses, which are cartilaginous joints, play a major role in craniofacial development including neurocranial expansion and facial outgrowth. Our previous data showed alterations in craniofacial structures with intrauterine exposure to nicotine. As the use of nicotine is increasing among youths, especially through use of electronic nicotine delivery systems, there is a great need to investigate the critical periods of nicotine exposure during pregnancy and postnatal development. Alterations in craniofacial growth that occur in response to maternal nicotine use must be understood in order to prevent debilitating conditions. For this investigation, we utilized cephalometric and histomorphometric analyses to investigate how nicotine exposure alters craniofacial development in offspring modeling maternal nicotine exposure either during pregnancy and lactation or post-partum lactation only compared with unexposed controls. Our results in mice showed significant changes in craniofacial dimensions and some specificity for effects in the synchondroses across the three experimental groups including significant changes in the cellular and the extracellular collagen matrix components of these growth centers. The most dramatic effects segregated to the lactation only exposed group, which is a major target from a prevention point of view as there is a common misconception among the public that nicotine cessation during pregnancy is sufficient for prevention of ill effects in the offspring.

The landscape for radioligand therapies in oncology

Combination chemotherapy and hormone therapy in patients with hormone receptor positive and HER2 negative metastatic breast cancer

Machine learning combining external validation to explore the immunopathogenesis of diabetic foot ulcer and predict therapeutic drugs

Diabetic foot ulcer (DFU) is a severe complication of diabetes, often leading to amputation due to poor wound healing and infection. The immune-related pathogenesis of DFU remains unclear, and therapeutic drugs are limited. This study aimed to explore the immune mechanisms of DFU and identify potential therapeutic drugs using machine learning and single-cell approaches. Through differential expression analysis of Gene Expression Omnibus (GEO) datasets, we identified 287 differentially expressed genes (DEGs), which were significantly enriched in IL-17 signaling and neutrophil chemotaxis pathways. Weighted gene co-expression network analysis (WGCNA) further pinpointed disease-associated modules containing 1,693 regulatory genes. Machine learning algorithms prioritized seven core genes—CCL20, CXCL13, FGFR2, FGFR3, PI3, PLA2G2A, and S100A8—with validation in an external dataset GSE147890 and single-cell sequencing revealing their predominant expression in neutrophils and keratinocytes. Immune infiltration analysis demonstrated significant dysregulation in DFU patients, characterized by elevated proportions of memory B cells, M0 macrophages, activated mast cells, and neutrophils. Potential therapeutic compounds were identified using the Connectivity Map database and tested through molecular docking and dynamics simulations. The study pinpointed selegiline, L-BSO, flunisolide, PP-30, and fluocinolone as promising therapeutic agents, offering new insights into the pathogenesis of diabetic foot ulcers (DFU) and potential therapeutic strategies.

Wafer-scale uniformity improvement of Dolan-bridge Josephson junction by shadow evaporation bias correction

Correction: Fluorescent reporter plasmids for single-cell and bulk-level composition assays in E. faecalis

Comparative metagenomics on community structure and diversity of rhizomicrobiome associated with monoculture and soybean precedent carrot

Monitoring, surveillance, antimicrobial resistance and genetic diversity analysis of non-typhoidal Salmonella in South Africa from 1960–2023 from animal and animal products

Salmonellosis remains one of the most frequently reported foodborne diseases globally, with the highest burden in low-resource areas. The millions of deaths caused by Nontyphoidal Salmonella (NTS) infections emphasize the urgent need for timely, detailed, and evidence-based interventions to effectively manage and monitor NTS burdens. This study retrospectively analyzed 1,028 NTS isolates from animals, the environment, and food products in South Africa, collected between 1960 and 2023. Among the 102 serotypes identified, S. Heidelberg, isolated only between 2000−2009 and 2020−2023, accounted for 94.3% of isolations during the latter period, suggesting a recent shift in Salmonella epidemiology in the region. The highest resistance rates were observed for cefoxitin (65.7%), cephalothin (62.8%), and tetracycline (59.8%), with a significant increase in resistance to several antibiotics, including ceftriaxone and aztreonam, from 2010−2023. Genetic analysis revealed that S. Gallinarium had the highest prevalence of antibiotic resistance genes, such as tetA (71.4%), qnrA (64.3%), cat1 (64.3%), blaPSE (57.1%), and both blaCMY-2 and qnrB at 50%. The blaPSE and blaSHV genes were strongly associated with ceftriaxone resistance in S. Dublin isolates, while blaPSE and qnrS were linked to chloramphenicol resistance in S. Enteritidis and S. Dublin isolates. Additionally, 87% of the virulence genes screened were present in over 50% of the serotypes, indicating increased adaptability and potential shifts in disease dynamics. The rise in antimicrobial resistance, driven by antimicrobial misuse, horizontal gene transfer, and biofilm formation, could alter serotype dynamics and changing disease epidemiology. This trend underscores the urgent need for effective antimicrobial stewardship and surveillance to combat the spread of antibiotic resistance in Salmonella populations.

Determinants and spatial patterns of solid fuel use in East Africa based on demographic and health survey data from 2012 to 2023

Static load test and bearing capacity analysis of broken line pretensioned prestressed concrete I-beam

The construction technology of broken line pretensioned method, which is suitable for long-span bridges, can greatly improve the flexural strength of concrete members. To study the mechanical performance and failure mode of broken line pretensioned prestressed concrete I-beam, an I-beam with a span of 30 m was taken as the research object and on-site static load tests were carried out. Based on the ABAQUS finite element software, the numerical simulation was carried out to analyze the mechanical properties and failure behavior of the I-beam under the concentrated load, and the ultimate flexural capacity of the I-beam was studied in combination with the theoretical analysis. In addition, the optimized arrangement of prestressed tendons was analyzed. The results show that in the on-site static load tests, the strain values at the mid-span section and 1/4-span basically show a linear growth trend, and the I-beam is always in the elastic stage during the tests. The numerical simulation results are in general agreement with the test data with regard to strain, displacement, and neutral axis position. When the concentrated load reaches 1910 kN, the prestressed tendons at the bottom of the I-beam enter the yield state. The prestressed tendons play a controlling role in the ultimate bearing capacity of the I-beam. The numerical simulation result of the ultimate bending moment in the mid-span section is 3.55% larger than the theoretical analysis result, and the theoretical calculation formulas tend to be conservative. When the prestressed tendons are arranged by the four-fold point method, the I-beam has higher stiffness and bearing capacity after concrete cracking. The research results can provide a reference for the design and construction of broken line pretensioned prestressed concrete I-beam.