Search Results (5,084)

Background: This prospective observational study was conducted to systematically assess immediate changes occurring (within one hour) in corneal endothelial cell morphology and anterior segment parameters following Nd:YAG laser posterior capsulotomy in pseudophakic patients and to analyze the correlation between these changes and laser energy parameters. Methods: A single-arm, within-subject pre–post design was employed to evaluate corneal endothelial morphology (cell density, count, area, coefficient of variation and hexagonal percentage) and anterior chamber parameters (depth, angle, volume) before and one hour after the procedure using specular microscopy and Pentacam analysis. Patient demographics (age), clinical parameters (best corrected visual acuity and intraocular pressure), postoperative-YAG laser interval, and laser energy parameters (energy per shot, pulse count, and total applied energy) were also documented. Results: Thirty-two pseudophakic patients (mean age 56.3 ± 19.2 years) underwent Nd:YAG laser posterior capsulotomy with mean energy per shot of 3.15 ± 1.07 mJ and pulse count of 34.3 ± 20.4. Specular microscopy revealed significant post-procedural decreases in endothelial cell density (2184.05 to 2057.2 cells/mm²; p = 0.006) and increases in average cell area (529.25 ± 242.72 to 587.75 ± 281.09 µm²; p = 0.004) and minimum cell area (199.3 ± 170.62 to 248.35 ± 202.7 µm²; p = 0.035). Corneal topography also decreased significantly in the anterior chamber angle (40.07 ± 10.34 to 35.42 ± 6.78 degrees; p = 0.048), with positive correlations between energy per shot and endothelial cell density (r = 0.557; p = 0.011) and average cell area (r = 0.544; p = 0.013). Conclusions: This study demonstrates that Nd:YAG laser capsulotomy causes immediate, energy-dependent alterations in corneal endothelial density and anterior chamber parameters within one hour post-procedurally. The identification of energy per shot as a key determinant represents a preliminary observation for optimizing laser parameters and reducing potential complications in pseudophakic patients. Full article

Background and Objectives: Urinary tract infections (UTIs) are a major cause of emergency department (ED) visits and hospital admissions among older adults. Although most seniors present hemodynamically stable, a sizeable fraction deteriorate during hospitalization, and no ED-specific tool exists to identify those at greatest risk. We sought to determine risk factors for in-hospital mortality in this population and to develop a predictive model. Materials and Methods: We analyzed the MIMIC-IV-ED database (2011–2019) and enrolled culture-confirmed UTI patients aged ≥ 65 years who were hemodynamically stable—defined as a systolic blood pressure ≥ 100 mm Hg without vasopressor support. Demographics, comorbidities, triage vital signs, and initial laboratory tests were extracted. Least Absolute Shrinkage and Selection Operator (LASSO) regression with 10-fold cross-validation was performed for variable selection. Discrimination was quantified with the C-statistic, calibration with the Hosmer–Lemeshow test, and clinical utility with decision curve analysis. Internal validation was assessed via 1000-sample bootstrap resampling. Results: Among 1571 eligible encounters (median age 79 years, 33% male), in-hospital mortality was 4.5%. LASSO selected eight variables; six remained significant in multivariable analysis: age, systolic blood pressure, oxygen saturation, white blood cell count, red cell distribution width, and blood urea nitrogen. The predictive nomogram demonstrated a C-statistic of 0.73 (95% CI 0.66–0.79) and outperformed traditional early warning scores. Conclusions: A six-variable nomogram may stratify mortality risk in hemodynamically stable older adults with UTI. Because the model was developed in a single U.S. tertiary-care ED, it remains hypothesis-generating until validated in external, multicenter cohorts to confirm generalizability. Full article

The genus Corynebacterium is commonly isolated from camel uteri, yet it is rarely identified to the species level. During our routine clinical examination of she-camels brought to the hospital with history of reproductive and systemic health issues, four isolates from the uterus and one isolate from blood could not be assigned to any valid Corynebacterium species. Therefore, we aim to identify these isolates, determine any potential virulence factors, and describe how gene turnover contributed to the evolution of these species. Genome-based and phenotypic identification, along with resistome, mobilome, virulome and phylogenomics analysis, was used to characterize the isolates. The isolates were Gram stain-positive, catalase-positive, and rod-shaped. The isolates were assigned to the genus Corynebacterium based on 16S rRNA gene sequence similarity and phylogenetic analysis. The isolates 3274 and ayman were classified as two new Corynebacterium species based on the average nucleotide identity (ANI) values of 78.46% and 68.88% and digital DNA–DNA hybridization (dDDH) values of 20.9% and 22.4%. The isolates 2581A, 2583C, and 4168A constitute a single Corynebacterium species based on their pairwise ANI value of 99% and dDDH value of more than 90%. In addition, isolates 2581A, 2583C, and 4168A showed ANI values of 75.99%, 75.86%, and 76.04% and dDDH values of 23.1%, 23%, and 22.5% with closely related species, and were designated as single new Corynebacterium species. Genes for mycolic acid and menaquinone biosynthesis were detected in all isolates. The isolates were susceptible to ceftiofur, linezolid, penicillin, erythromycin, and tetracycline. All isolates harbored the antiseptic resistance gene qacA. Moreover, virulence factors involved in cell adhesion and iron acquisition were detected. The evolution of these species is dominated by gene gain rather than gene loss. The majority of these genes are acquired through horizontal gene transfer, mediated by prophages and genomic islands. In summary, we characterized three new Corynebacterium species, expanding the number of new Corynebacterium species from animals. Moreover, we described the mechanism underlying the genome evolution of these new species. The clinical findings and detection of virulence genes highlight the significance of these isolates as possible pathogens, contributing to the development of endometritis in camels. Full article

Basal stem rot caused by Fusarium solani is among the most destructive soil-borne diseases affecting passion fruit (Passiflora spp.). While biological control employing antagonistic microorganisms offers a promising plant protection strategy, reports on antagonists specifically targeting passion fruit basal stem rot remain limited. Here, a screen for F. solani antagonists led to the identification of Bacillus velezensis strain L11-7, whose whole genome was subsequently sequenced. Pot experiments demonstrated that strain L11-7 significantly reduced the severity of stem basal rot, achieving control efficiencies of 92.85%, and exhibited broad antagonistic properties against other plant pathogenic fungi. L11-7 possesses cellulase, glucanase, and protease activities, alongside capabilities for nitrogen and phosphorus production. L11-7 was identified as B. velezensis through morphological analysis, 16S rRNA, gyrB, and rpoB gene sequencing, and whole-genome analysis. Its genome features a single circular 3.97 Mb chromosome harboring 13 s metabolite biosynthetic gene clusters (e.g., fengycin, surfactin, macrolactin H, bacillaene, difficidin) and genes encoding essential cell wall hydrolases. Several genes related to plant growth promotion, including those involved in nitrogen fixation and IAA production, are also present. These results indicate that B. velezensis L11-7 is a prospective biocontrol agent against passion fruit basal stem rot and has plant growth-promoting properties. Full article

Background: The progression of osteosarcoma is closely related to the immune microenvironment. Related studies have found that the RNA-binding motif protein, X-linked (RBMX), plays a regulatory role in modulating the biological characteristics of the tumor microenvironment (TME). However, its regulatory mechanism in osteosarcoma remains unclear. Methods: In this study, the expression of RBMX in osteosarcoma was analyzed using the results of bulk and single-cell transcriptome sequencing of human osteosarcoma. The RBMX knockout cell line was constructed via lentivirus transfection. The mouse subcutaneous implantable tumor model and single-cell transcriptome sequencing analysis revealed the effects of RBMX on the osteosarcoma microenvironment, as verified via multiplex immunofluorescence, flow cytometry, and PCR experiments. Results: Using the TARGET database and multiplex immunofluorescence, we found that RBMX is highly expressed in human osteosarcoma and is associated with poor prognosis. The high expression of RBMX may mediate the immunosuppressive microenvironment of human osteosarcoma. In vitro cell experiments showed that knockout of RBMX significantly inhibited the proliferation of mouse osteosarcoma cells. Through single-cell transcriptome sequencing analysis of subcutaneous implantable tumors in mice, we determined that RBMX deletion substantially elevated the recruitment of cytotoxic CD8⁺T cells within the mouse TME, which was further verified through flow cytometry analysis. Cell coculture assay confirmed that knockout of RBMX significantly enhanced the cytotoxic activity of CD8⁺T cells. Finally, cell communication and in vitro experimental verification revealed that knocking out RBMX might enhance the infiltration of CD8⁺T cells by upregulating histocompatibility 2, K1, and K region (H2-K1) and downregulating thrombospondin 1 (THBS1). Conclusions: This study may provide potential targets for reshaping the immune microenvironment of osteosarcoma and improving its therapeutic efficacy. Full article

In this study, we examine the presence of bias in weighted least squares (WLS) estimation within the context of first-order bifurcating autoregressive (BAR(1)) models. These models are widely used in the analysis of binary tree-structured data, particularly in cell lineage research. Our findings suggest that WLS estimators may exhibit significant and problematic biases, especially in finite samples. The magnitude and direction of this bias are influenced by both the autoregressive parameter and the correlation structure of the model errors. To address this issue, we propose two bootstrap-based methods for bias correction of the WLS estimator. The paper further introduces shrinkage-based versions of both single and fast double bootstrap bias correction techniques, designed to mitigate the over-correction and under-correction issues that may arise with traditional bootstrap methods, particularly in larger samples. Comprehensive simulation studies were conducted to evaluate the performance of the proposed bias-corrected estimators. The results show that the proposed corrections substantially reduce bias, with the most notable improvements observed at extreme values of the autoregressive parameter. Moreover, the study provides practical guidance for practitioners on method selection under varying conditions. Full article

Microbial-enhanced oil recovery (MEOR) is a promising technology for oilfield development. To improve MEOR efficiency, two functional strains—Bacillus mucilaginosus ZZ-8 and Bacillus amyloliquefaciens ZZ-11—were isolated and purified. The growth characteristics, biosurfactant production, and crude oil emulsification performance of these strains were systematically evaluated through single-strain cultures and a co-culture system (ZZ-8: ZZ-11 = 1:1). The results demonstrated that the co-culture system exhibited superior growth and functional performance compared to monocultures. The cell-free supernatant significantly reduced oil–water interfacial tension, decreasing the contact angle from 53.56 ± 1.3° to 28.78 ± 0.82°, thereby enhancing crude oil detachment from rock surfaces and improving oil displacement efficiency. Gas chromatography (GC) analysis further confirmed the co-culture system’s pronounced degradation of long-chain alkanes (C17–C35). In oil sand washing experiments, the 1:1 mixed-strain fermentation broth achieved a crude oil elution rate of 84.39%, representing an 89.80% increase over uninoculated medium. This study not only validates the synergistic effect of the B. mucilaginosus–B. amyloliquefaciens co-culture system in enhancing oil recovery but also provides a theoretical foundation and innovative strategy for its practical application in MEOR technology. Full article

This paper presents a thermal study of a lithium-ion traction battery with different cooling configurations during simulated city driving and high-power charging. Four liquid cooling configurations—single or triple plates with straight or U-shaped tubes—were evaluated using finite element models in the Q-Bat Toolbox for MATLAB. Simulations were conducted using the Worldwide Harmonized Light Vehicles Test Cycle (WLTC) and a high-current charging profile based on the CHAdeMO standard (up to 400 A). The results indicate that while cooling is not strictly necessary under typical driving conditions, it significantly improves thermal stability and reduces peak temperatures. The best configuration reduced peak cell temperatures by 1.96% during driving and by 16% during fast charging. The cooling system also minimized temperature gradients within the battery, reducing the risk of degradation. Box-plot analysis confirmed that an efficient cooling system stabilizes the temperature distribution and smooths out extreme values. The results highlight the importance of thermal management for extending battery life and ensuring safe operation, particularly during fast charging conditions. Full article

Cutaneous T-cell Lymphomas (CTCLs) are a heterogeneous group of non-Hodgkin lymphomas that currently have an incompletely understood pathophysiology and several challenges in both diagnosis and management. Single-cell RNA sequencing (scRNA-seq) is a powerful tool that enables the analysis of gene expression at the individual-cell level, revealing cellular heterogeneity and a complex tumor microenvironment. As single-cell RNA sequencing has become increasingly utilized, we aimed to provide an update on recent notable applications of single-cell RNA sequencing in CTCL and their findings. The included studies highlight the intricate network of interactions in the tumor microenvironment that contributes to tumorigenesis. While CTCL is notoriously heterogeneous, our results identify key markers that prove promising for diagnosis, prognostication, and therapeutic targets. Full article

Background/Objectives: Neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, has prognostic value in non-small cell lung cancer (NSCLC), but its longitudinal performance in routine care is unclear. We evaluated baseline and 12-month changes in NLR and hemoglobin in a single-center, Eastern European cohort. Methods: In this retrospective study, 180 adults with histologically confirmed NSCLC, diagnosed May 2022–April 2024 at a Romanian tertiary center, were followed until 30 April 2025. Baseline demographics, tumor characteristics, molecular profiles, laboratory parameters, and treatments were extracted from electronic health records. Progression-free survival (PFS) was the primary endpoint, overall survival (OS) the secondary, analyzed using Kaplan–Meier curves and Cox proportional hazards models. An additional treatment-start-anchored sensitivity analysis in treated patients was conducted. Results: The cohort (median age 67.8 years, 68.9% stage IV) received chemo-immunotherapy (58.9%), immunotherapy (26.7%), chemotherapy (9.4%), or supportive care (5.0%). Median for PFS was 8.2 months and for OS 14.5 months. A high baseline NLR (≥3, 58.9%) increased progression risk (HR 1.60, 95% CI 1.10–2.32, p = 0.014), with a trend for worse OS (HR 1.45, 95% CI 0.99–2.12). A 12-month NLR increase (62.2%) further elevated progression risk (HR 1.52, 95% CI 1.05–2.20, p = 0.026). Low hemoglobin (<12 g/dL) had a non-significant effect (HR 1.38, 95% CI 0.97–1.96, p = 0.074). PD-L1 ≥ 50% and chemo-immunotherapy correlated with longer PFS. Findings were consistent in the treatment-start anchored sensitivity analysis. Conclusions: These exploratory findings suggest that inexpensive hematologic markers can complement clinical assessment in advanced-stage NSCLC; prospective multi-center validation is warranted. Full article

The hydrogen fuel cell vehicle (HFCV) market is growing rapidly, but technological limitations, high costs, and market constraints are hindering enterprise performance. Existing studies often analyze isolated factors, overlooking their configurational interactions. This study applies the Technology–Organization–Environment (TOE) framework and fuzzy-set Qualitative Comparative Analysis (fsQCA) to examine how R&D capability, human capital level, scale of enterprise, attention allocation, and government support shape high performance in 40 Chinese HFCV enterprises. The consistency of all antecedents does not exceed 0.9, indicating that high performance does not depend on any single factor. The sufficiency analysis identifies three effective configurations: technology-driven, internal–external synergy, and organization–policy-driven, with an overall solution consistency of 0.9206 and a coverage of 0.4167. Without adequate government support and human capital, achieving high performance in HFCV enterprises appears improbable. These findings reveal multiple pathways toward high performance and highlight the importance of condition combinations over isolated effects, offering theoretical and practical insights into sustainable development strategies for emerging green industries. Full article

Introduction: Bovine leukemia virus is a single-stranded RNA virus that targets B cell CD5⁺ lymphocytes in cattle. Only a tiny percentage of individuals develop malignant lymphoproliferative disorders, while most remain healthy carriers or experience persistent lymphocytosis. The exact mechanisms leading to lymphoma development are complex and not fully understood. RNA-seq analysis of cows’ peripheral blood leukocytes (PBLs) with and without Bovine leukemia virus (BLV) antibodies was conducted to gain a deeper understanding of molecular events beyond BLV infection. Method: Eighteen samples were selected, and their RNA was sequenced. For gene expression analysis and protein–protein network interactions, three groups were selected, including healthy negative samples (CT, n = 7), asymptomatic carriers (AC, n = 5), and persistent lymphocytosis (PL, n = 6), to provide the differentially expressed gene (DEG) and protein–protein interaction network (PPIN) outputs. Results: Our results demonstrated that in comparison to CT, ACs upregulated TLR7 and transcription activation factors. In the CT vs. PL group, MHC class II, transcription activation factors, and anti-inflammatory cytokines increased, while the acute-phase proteins, antiviral receptors, and inflammatory cytokines decreased. Additionally, antiviral receptors, acute-phase proteins, and inflammatory receptors were downregulated in the PL versus the AC groups. Moreover, PPINs analysis suggested that nuclear receptor corepressor 1 (NCOR1), serine/arginine repetitive matrix 2 (SRRM2), LUC7 like 3 pre-mRNA splicing factor (LUC7L3), TWIST neighbor (TWISTNB), U6 small nuclear RNA and mRNA degradation associated (LSM4), eukaryotic translation elongation factor 2 (EEF2), ubiquitin C (UBC), CD74, and heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNP A2B1) are possible hub gene candidates in the PL group. Conclusions: Our results suggest that innate and cellular immune responses are more loose in severe BLV infectious conditions, while the PPINs revealed that new protein interactions are necessary for oncogenesis. Full article

Background: The SUMO E3 ligase PIAS1 (Protein Inhibitor of Activated STAT1) regulates pathways such as TGFβ signaling and has been implicated in multiple cancers. However, its role in the tumor microenvironment (TME), particularly in non-malignant stromal and immune cells, remains poorly understood. This study aimed to characterize the expression and functional relevance of PIAS1 within the TME of oral squamous cell carcinoma (OSCC). Methods: PIAS1 protein expression was assessed via immunohistochemistry (IHC) on OSCC tissue microarrays. Single-cell RNA-sequencing (scRNA-seq) datasets from OSCC tumors and normal tissues were analyzed to map cell-type-specific PIAS1 expression. Downstream effects were evaluated using differential gene expression, Ingenuity Pathway Analysis (IPA), gene set enrichment analysis (GSEA), and cell–cell communication inference. Results: IHC analysis revealed that higher stromal PIAS1 levels correlated with improved survival. scRNA-seq analysis showed an increase in the proportion of PIAS1-expressing cells across most stromal and immune cell populations within OSCC-derived tumors compared to their counterparts in adjacent normal tissue. However, when comparing PIAS1-positive cells, expression levels were significantly reduced in cancer cells, CAFs, TAMs, T cells, and endothelial cells within the TME. PIAS1-positive CAFs, TAMs, and T cells exhibited activation of apoptotic and tumor-suppressive pathways, while PIAS1-negative counterparts showed enrichment of immunosuppressive signaling and immune checkpoint expression. Cell–cell communication analyses indicated that PIAS1 fosters an immune-activated TME by promoting pro-inflammatory signaling, M1-like TAM polarization, and T cell activation. Conclusions: PIAS1 expression in stromal and immune cells is associated with tumor-suppressive reprogramming of the OSCC microenvironment. These findings position PIAS1 as a potential modulator of anti-tumor immunity and candidate target for therapeutic intervention. Full article

Congenital heart disease (CHD) is associated with neurodevelopmental and cognitive impairments, but the underlying molecular mechanisms remain unclear. This study investigated cardiac neuronal genomics in CHD using single-nucleus RNA-sequencing data (GSE203274) from 157,273 cardiac nuclei of healthy donors and patients with hypoplastic left heart syndrome (HLHS), Tetralogy of Fallot (TOF), dilated (DCM), and hypertrophic (HCM) cardiomyopathies. The Uniform Manifold Approximation and Projection (UMAP) clustering identified major cardiac cell types, revealing neuron-specific transcriptional programmes. Neuronal populations showed enriched expression of neurodevelopmental disorder-linked genes (NRXN3, CADM2, ZNF536) and synaptic signalling pathways. CHD cardiac neurons exhibited upregulated markers of cognitive dysfunction (APP, SNCA, BDNF) and neurodevelopment regulators (DNMT1, HCFC1) across subtypes. Cardiomyocyte troponin elevation correlated with neuronal exosome receptor expression (TLR2, LRP1), suggesting intercellular communication. Gene ontology analysis highlighted overlaps between cardiovascular disease pathways and neurodevelopmental disorder signatures in CHD neurons. These findings provide the first neuro-genomic map of cardiac neurons in CHD, linking cardiac pathology to neural outcomes through transcriptional dysregulation. Further, the systemic analysis of clinical findings in CHD further supports the risk of neurodevelopmental impacts. In summary, this study identifies transcriptional dysregulation within cardiac neurons in CHD and, together with a systemic analysis of clinical data, provides molecular evidence linking cardiac pathology to neurodevelopmental and cognitive impairments. Full article

Malignant bone and soft tissue tumors are often resistant to conventional treatment, and treatment options for unresectable and metastatic cases are limited. L-type amino acid transporter 1 (LAT1) is overexpressed in several malignancies, including sarcomas, making it an attractive target for targeted alpha therapy. In this study, we investigated the therapeutic efficacy of LAT1-targeted alpha therapy using a novel modified 3-astatin-211 Astato-α-methyl-L-tyrosine (²¹¹At-AAMT) for bone and soft tissue sarcomas. LAT1 expression and the specificity of LAT1-mediated uptake of ²¹¹At-AAMT were evaluated in bone and soft tissue sarcoma cell lines. Antiproliferative effects were assessed using cell viability and colony formation assays. DNA damage was assessed using immunostaining with phosphorylated histone γH2AX. In vivo efficacy of ²¹¹At-AAMT, determined using xenograft mouse models, was compared with that of doxorubicin. LAT1 was highly expressed in all cell lines, especially MP-CCS-SY and MG-63 cells. ²¹¹At-AAMT uptake was LAT1-dependent and significant in all cell lines. It inhibited cell proliferation in a dose-dependent manner, comparable to that of doxorubicin. In xenograft models, a single administration of ²¹¹At-AAMT significantly inhibited tumor growth without systemic toxicity, whereas doxorubicin caused weight loss. Histopathological analysis showed reduced cell density, inhibited proliferation, and extensive DNA damage in tumors treated with ²¹¹At-AAMT, whereas LAT1 expression was maintained in residual tumor tissues. LAT1-targeted alpha therapy with ²¹¹At-AAMT demonstrated antitumor efficacy comparable to that of first-line chemotherapy for osteosarcoma and soft tissue sarcoma. Sustained LAT1 expression suggests the potential for repeated or combination treatments, highlighting its promise as a novel therapy for advanced, treatment-resistant sarcomas. Full article