Search Results (3,590)

This study aims to verify whether there is a statistically significant relationship between COVID-19 mortality rates, the Human Development Index (HDI), and population age across the World Health Organisation (WHO) member states. Despite the extensive literature on COVID-19 mortality and socio-demographic indicators, few studies explicitly integrate count data diagnostics, zero-inflation mechanisms, and multilevel longitudinal modelling to jointly capture cross-country heterogeneity and temporal dynamics. This study addresses this gap by applying a structured modelling framework that combines negative binomial, zero-inflated, and multilevel regression models to the WHO country-level data. For this purpose, two different statistical techniques were applied, namely: negative binomial regression modelling, zero-inflated negative binomial type for daily temporal exposure on 20 July 2020 and 20 July 2022, before and after the application of the first dose of the COVID-19 vaccine; and multilevel regression for two-level repeated measures data. Negative binomial regression estimates indicate statistically significant positive associations between HDI, age, and COVID-19 mortality rates before the application of the first dose of the vaccine. The variance decomposition from the definition of an unconditional model indicates significant variability in the occurrences of infection and death and between countries/states over time. Full article

Fusarium verticillioides is a significant agricultural pathogen and an emerging causative agent of invasive fusariosis in clinical settings. Fusarium species frequently exhibit resistance to available antifungal agents, yet the molecular mechanisms underlying azole resistance remain poorly characterized. In this study, we identified the Zn(II)₂Cys₆ transcription factor FvADS-1 as a positive regulator of the azole stress response in F. verticillioides. The transcription of FvADS-1 was significantly induced by ketoconazole (KTC), and its deletion increased susceptibility to multiple azole compounds. Mechanistically, FvADS-1 positively regulates the KTC-induced expression of genes encoding ABC transporters and ergosterol biosynthesis enzymes, thereby modulating intracellular KTC accumulation and sterol homeostasis under azole stress. Furthermore, FvADS-1 positively regulates the transcriptional response of peroxisomal genes and contributes to fungal tolerance to oxidative stress. Notably, deletion of FvADS-1 attenuates the virulence of F. verticillioides on maize. The function of ADS-1 is evolutionarily conserved: heterologous expression of N. crassa ads-1 restored azole resistance in FvADS-1 deletion mutant, and the deletion of the F. oxysporum homolog FoADS-1 similarly increased azole susceptibility. Collectively, our study demonstrates that the conserved transcription factor ADS-1 plays a central role in regulating azole resistance and virulence in the pathogen F. verticillioides, offering new insights into antifungal resistance mechanisms in pathogenic filamentous fungi. Full article

Bixlozone has significant potential as a pre-emergence and early post-emergence herbicide in wheat production across China. However, its safety when applied to wheat is poor, frequently causing phytotoxicity. This study confirmed the capacity of pyroxsulam to mitigate bixlozone-induced injury without compromising weed control efficacy and examined the underlying processes. Wheat exposed to bixlozone alone developed pronounced chlorosis and significant reductions in tiller formation, ultimately lowering the grain yield. In contrast, co-treatment with pyroxsulam substantially relieved chlorosis and restored both the tiller number and yield performance. Bixlozone reduced chlorophyll and carotenoid levels, impairing the function of photosystem II (PSII), which was mitigated by pyroxsulam application. Transcriptome profiling showed that pyroxsulam strongly activated detoxification-related pathways, especially those associated with glutathione S-transferases (GSTs) and ATP-binding cassette (ABC) transporters, which facilitate the metabolic detoxification or compartmentalization of bixlozone. qRT-PCR further validated the marked induction of key detoxification genes ABCC8-X1, GSTU6 and ABCC10 following pyroxsulam addition. Collectively, this study provides initial mechanistic insight into how pyroxsulam, though itself a herbicide, can enhance wheat tolerance to bixlozone by stimulating endogenous detoxification systems. These findings offer a framework for the development of safer herbicide mixtures and expand current understanding of crop–herbicide interactions, providing meaningful implications for herbicide management and sustainable agricultural systems. Full article

Diffuse large B-cell lymphoma (DLBCL) is a common, aggressive non-Hodgkin lymphoma with significant molecular heterogeneity. This variability arises in part from its distinct molecular subtypes, including germinal center B-cell-like (GCB) DLBCL, activated B-cell-like (ABC) DLBCL, and primary mediastinal B-cell lymphoma (PMBL), which differ markedly in their genetic profiles, signaling pathway activities, and clinical outcomes. Although rituximab-based R-CHOP regimens have significantly improved patient outcomes, around 40% of patients still experience relapsed or refractory disease. DLBCL cells sustain their rapid proliferation through the establishment of an intricate lipid metabolism regulatory network. The interplay between this network, cell death mechanisms (e.g., ferroptosis), and the tumor immune microenvironment (TIME) significantly impacts the malignant progression of the disease and its resistance to treatment. This review summarizes recent advances in understanding the molecular mechanisms and interplay among these processes in DLBCL and discusses the clinical relevance of associated prognostic biomarkers, thus providing new insights into the development of precision therapies. Full article

DLBCLs constitute an aggressive type of lymphoma with varied clinical, molecular and genetic features. The cells are characterized by NFkB pathway disturbances and BCL-2 and mTOR protein deregulation, which significantly inhibit apoptosis. Hence, many treatment strategies have been established to target the functioning of these pathways. While early clinical trials have found mTOR, NFkB and Bcl-2 inhibitors to have activity in many hematological cancers, their activity as monotherapy agents may still be insufficient; therefore, combinations of these compounds with other molecules demonstrating activity in a given cancer subtype are under evaluation. In vitro studies were conducted on the Riva (ABC subtype) and Toledo (GCB subtype) cell lines. Three novel drugs were administered: AZD2014 (vistusertib)—an inhibitor of the serine–threonine kinase mTOR; IMD-0354—an NFκB inhibitor; and ABT-199 (venetoclax)—a highly selective inhibitor for BCL-2. Drugs were administered alone, in pairs and as a combination of all three agents. For the Riva cell line, ABT-199 had the strongest pro-apoptotic effect on cancer cells as monotherapy. As pairs, AZD2014+ABT-199 and ABT-199+IMD0354 demonstrated similar effects. The combination of the three drugs did not have a stronger effect than the drug pairs. For the Toledo cell line, no significant differences were noted between the drugs when used as monotherapy. In pairs, the strongest effect was observed for AZD2014+ABT-199; furthermore, this effect was not intensified by the combination of the three drugs. Our findings, including those for the BCL-2 and mTOR inhibitors, indicate that there is a need for further in vivo studies to evaluate these drugs as potentially effective treatments for DLBCL of the ABC and GCB subtypes. Full article

Roads impact medium- and large-sized mammal populations through both collisions and barrier effects. This study examined how landscape characteristics influence roadkill occurrences along the Dom Pedro I highway (SP-065), located in the Cantareira-Mantiqueira Corridor, São Paulo State, Brazil. The SP-065 crosses important remnants of the Brazilian Atlantic Forest, a global hotspot for biodiversity. Roadkill records were obtained from the Environmental Company of the State, and land use data were extracted from the MapBiomas platform. We analyzed seven landscape variables (in percentage): native forest, pasture, agriculture, forestry, urban areas, mosaic of uses, and water bodies, considering multiple spatial scales. Mammal species were grouped functionally by home range size and tolerance to anthropogenic environments. In total, 1418 roadkills of 24 species were recorded, including eight threatened species. Capybaras (Hydrochoerus hydrochaeris) were the most frequently killed species. Generalized linear models showed that, for Group G1 (small home range, common in human-modified areas), roadkills were positively associated with native forest and pasture, and negatively with mosaic landscapes. For Group G3 (large home range, tolerant to anthropogenic areas), agriculture had a positive effect, especially within a 3000 m radius. For Group G5 (capybara), roadkills increased with pasture and agriculture, while mosaic uses had a negative effect. Since pasture and agriculture were frequently linked to higher roadkill rates, environmental impact assessments should consider these land-use types when planning mitigation actions. Ultimately, responsibility for roadkill extends beyond highway managers to rural landowners and local governments, as land-use patterns around roads strongly influence mammal movement and mortality. Full article

The tooth flank distortion error occurring during the form-grinding (FG) of an involute helical gear can significantly compromise transmission performance. Conventional research approaches often focus on single-parameter optimization—either the grinding wheel installation angle (GWIA) or the contact line (CL)—without adequately accounting for the coupling relationships among GWIA, CL, and the modification curve (MC). To address this limitation, this study proposes an innovative joint optimization approach that simultaneously optimizes GWIA, CL, and MC to effectively minimize tooth flank distortion in FG. Based on the principles of form-grinding, a mathematical model is established for the contact line of the target gear and the cross-sectional profile of the grinding wheel. The relationship between GWIA and tooth flank deviation is investigated using a proprietary virtual prototype. A multi-objective artificial bee colony (ABC) optimization algorithm is employed to determine the optimal values of GWIA and CL. For the axial modification curve, this paper introduces a novel three-segment quadratic curve optimization scheme as an improvement over conventional modification methods. To validate the proposed optimization technique, form-grinding experiments are conducted on the L300G gear grinding machine. Simulation outcomes indicate that, pre-optimization, the maximum tooth flank distortion errors primarily occur at the tooth root and tip regions on both ends of the gear. After optimization, the simulated distortion error on the left tooth flank is reduced by 48.5%, while the right flank shows a reduction of 29.4%. These simulation outcomes exhibit a deviation of approximately 10% compared with the experimental results. This study provides valuable insights for enhancing the transmission performance of helical gears. Full article

Accurate inversion of the deep initial in situ stress field is a fundamental prerequisite for stability analysis of surrounding rock in underground engineering, roadway support design, and prevention and control of dynamic disasters. To address the problems of scarce in situ stress measurements in deep mining areas, the inability of conventional regression methods to capture the nonlinear characteristics of complex tectonic stress fields, and the tendency of traditional inversion algorithms to fall into local optima and overfitting, this paper proposes an intelligent inversion method based on support vector regression optimized by the artificial bee colony algorithm (ABC-SVR). The artificial bee colony algorithm is employed to adaptively optimize the core parameters of the SVR model, thereby enabling high-precision inversion of complex deep stress fields. Comparing the results with acoustic emission tests demonstrated that the ABC-SVR model significantly outperforms conventional SVR and backpropagation neural networks across various performance metrics. The inversion results show high consistency with the measured data, achieving a root mean square error (RMSE) of 1.25, a mean absolute percentage error (MAPE) of 4.16%, and a coefficient of determination (R²) of 0.908. This method can rapidly reconstruct high-precision initial in situ stress fields in deep unmined regions, providing highly reliable boundary conditions for numerical simulations and demonstrating significant engineering application potential. Full article

South China’s freshwater biodiversity has been shaped by Quaternary climatic oscillations and persistent geological barriers. We investigated the phylogeography and conservation implications of the primary freshwater fish Microphysogobio kachekensis across mainland China and Hainan Island using mitochondrial (cyt b and control region) and nuclear (RAG2 and rpS7-1) markers from 200 individuals. Mitochondrial analyses recovered two major lineages and multiple sublineages largely structured by drainage basins, whereas nuclear data resolved four geographically concordant lineages. Population differentiation was strong (high F_ST), and SAMOVA/AMOVA supported major barriers restricting gene flow, including the Qiongzhou Strait, Gulf of Tonkin, Yunkai Mountains, and Nanling Mountains. Ancestral-area reconstruction inferred the Pearl River region as the most likely source area, followed by dispersal to northern Hainan and subsequent expansion to southern Hainan and the Red River, with additional northward expansion to the Zhejiang–Fujian region. Despite high haplotype diversity, within-population nucleotide diversity was low, consistent with long-term river isolation and complex demographic history. We propose six ESUs and four MUs for evolutionarily informed conservation and to guide stock enhancement in southern China. Full article

Breast cancer (BC) is the most common malignant disease in women in Romania, with incidence and mortality rates among the highest in Europe. This consensus statement aims to ensure equitable access to care for human epidermal growth factor receptor 2-negative metastatic BC (HR+/HER2– mBC) and triple-negative mBC (mTNBC) in Romania. Between December 2024 and June 2025, a scientific board of 11 oncologists, in collaboration with the Romanian National Society for Medical Oncology (SNOMR), developed national recommendations based on ESMO/NCCN/ABC guidelines, clinical expertise, and local conditions. A modified Delphi survey was conducted among medical oncologists to evaluate acceptance of recommendations with greatest clinical impact. Key recommendations included: mandatory biopsy at metastasis with ER/PgR/HER2 retesting, HER2-low assessment, and molecular profiling (BRCA, PIK3CA, AKT1/PTEN, ESR1, plus PD-L1 testing in mTNBC); for HR+/HER2– mBC, first-line endocrine therapy plus CDK4/6 inhibitor, followed by targeted agents, chemotherapy, or antibody–drug conjugates based on progression and visceral crisis; for mTNBC, first-line immune checkpoint inhibitor plus chemotherapy in PD-L1-positive, PARP inhibitors in BRCA-positive patients, and sacituzumab-govitecan or trastuzumab-deruxtecan later; systematic toxicity monitoring; and integrated supportive and palliative care. Sixty-one oncologists completed the survey, with >90% overall agreement, suggesting broad acceptance of recommendations as Romania’s national standard for mBC care. Full article

Background/Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B-cell hyperactivation and excessive autoantibody production. Z-DNA binding protein 1 (ZBP1), an innate immune sensor involved in nucleic acid recognition and cell death signaling, has been implicated in antiviral and inflammatory responses. However, its role in B-cell dysregulation during SLE remains unclear. Methods: Integrative transcriptomic analyses were performed using public datasets (GSE61635, GSE235658, GSE136035, and GSE163497) to determine the expression pattern and biological functions of ZBP1 in SLE. Bulk RNA-seq and single-cell RNA-seq data were used to evaluate ZBP1 expression across B-cell subsets. Correlations between ZBP1 expression, disease activity, and immunological parameters were assessed. RNA-seq data following ZBP1 knockdown were analyzed to explore its potential downstream pathways and molecular networks. In addition, in vitro ZBP1 knockdown experiments were conducted to examine its effects on B-cell activation, plasma cell differentiation, and antibody production. Results: ZBP1 was significantly upregulated in peripheral blood and B cells from SLE patients and was enriched in pathways related to type I interferon signaling and cytokine-mediated immune responses. Single-cell transcriptomic profiling further revealed elevated ZBP1 expression across multiple B-cell subsets, including naïve B cells, memory B cells, age-associated B cells (ABCs), and plasma cells. Clinically, ZBP1 expression in peripheral B cells was positively correlated with CD86 mean fluorescence intensity (MFI), SLE Disease Activity Index (SLEDAI) scores, and serum IgG levels, suggesting a link between ZBP1 and B-cell activation. RNA-seq analysis following ZBP1 silencing demonstrated that ZBP1 regulates genes involved in the cell cycle, DNA replication, and p53 signaling, indicating its potential role in promoting B-cell proliferation and activation. Functionally, ZBP1 silencing impaired B-cell activation, reduced plasma cell differentiation, and decreased immunoglobulin production in vitro. Conclusions: Our study identifies ZBP1 as a molecule upregulated in SLE B cells and associated with B-cell activation and disease activity. Although direct causality remains to be established, the data indicate that ZBP1 may contribute to SLE pathogenesis by modulating cell cycle-related pathways and promoting aberrant B-cell responses, highlighting its potential as a biomarker and a candidate therapeutic target in SLE. Full article

This paper addresses the challenge of simultaneous arrival for UAV clusters and proposes a route planning method based on an enhanced Non-dominated Sorting Genetic Algorithm III (NSGA-III). Initially, the paper defines the simultaneous arrival problem and formulates the corresponding mathematical model, considering the complexity of multi-objective optimization in UAV clusters. A novel path generation framework is introduced, which incorporates multiple optimization objectives—such as time coordination, threat mitigation, and resource consumption—aimed at improving flight safety, efficiency, and resource management. To enhance the algorithm’s search performance, a hybrid approach combining the Artificial Bee Colony (ABC) algorithm with NSGA-III is proposed. This improved NSGA-III strategy overcomes the limitations of the original algorithm in managing complex constraints and multi-objective optimization problems, resulting in significant improvements in search accuracy and convergence speed. Finally, the performance of the improved algorithm is evaluated through simulations and compared with traditional methods. The results show that the proposed approach optimizes flight time, reduces resource consumption, and effectively mitigates threats, all while ensuring the simultaneous arrival of UAV clusters. Full article

This study employs the Atangana–Baleanu–Caputo fractional derivative within the Moore–Gibson–Thompson heat conduction model to analytically investigate the thermoelastic vibrations in solid medium-containing voids. The ABC–MGT formulation incorporates a non-singular Mittag–Leffler memory kernel, facilitating the modeling of tempered hereditary relaxation in voided thermoelastic media, thereby producing more realistic attenuation and phase lag characteristics in transient responses than conventional integer-order models. Specifically, our novelty lies in developing a coupled thermoelastic–void formulation within an ABC–MGT heat conduction framework, deriving the full governing system and boundary-value solution in the Laplace domain, and providing a systematic parametric analysis showing how the ABC order changes attenuation, phase lag, and stress/void interactions. This approach enables a precise analytical resolution of the problem. The analysis indicates that the presence and size of voids substantially impact the system response variables, with smaller apertures yielding reduced magnitudes. Thus, this analytical investigation introduces a novel methodology for addressing the complex challenges associated with advanced functional materials and high-performance engineering structures. Full article