Search Results (40,054)

Gastric cancer remains a leading cause of cancer-related mortality worldwide and is marked by pronounced molecular heterogeneity. Advances in genomic profiling have identified key genetic alterations, including oncogenes (HER2, PIK3CA, and MYC), tumor suppressor genes (TP53, CDH1, and ARID1A), and regulators of genome stability and cell architecture (MLH1, RHOA, and CLDN18), which have driven the development of targeted therapeutic strategies. Although genetically engineered mouse models and xenograft systems have been indispensable for functional validation and preclinical drug testing, many approaches that showed promising efficacy in animal models—such as inhibition of EGFR, MET, FGFR2, and the PI3K pathway—failed to translate into overall survival benefits in clinical trials, highlighting major translational limitations. In contrast, HER2- and CLDN18.2-targeted therapies represent rare but notable clinical successes, underscoring the importance of true oncogenic dependency, precise biomarker-driven patient selection, and robust preclinical validation. In this review, we systematically categorize gastric cancer-associated genes according to their biological functions, summarize representative animal models, and critically examine key successes and failures in clinical translation, emphasizing the need for biologically faithful models and precision-driven translational strategies. Full article

This study combined experimental analysis with deep learning to investigate the effects of curing age, steel slag content, and gradation composition on the mechanical properties of cement-stabilized steel slag (CSSS). The strength evolution patterns and underlying microscopic mechanisms were systematically elucidated. Experimental results showed that CSSS strength grows nonlinearly with curing age, with optimal mechanical performance achieved at a 60% steel slag content. The microstructural evolution characterized by SEM-EDS and XRD revealed that steel slag incorporation promotes the formation of AFt and densifies the gel network. In later curing stages, natural carbonation of Ca(OH)₂ and secondary hydration of reactive steel slag components produce CaCO₃ and additional C-S-H gel, which fill pores and significantly enhance long-term strength. A CNN-GRU-Attention model was developed to predict the unconfined compressive strength (UCS) and splitting tensile strength (STS) of CSSS. In a single data split, the model achieved R² values of 0.9875 for UCS and 0.9911 for STS, with RMSEs of 0.2577 MPa and 0.0234 MPa, and MAEs of 0.2059 MPa and 0.0184 MPa, outperforming all benchmark models. Under rigorous 5 × 5 repeated cross-validation, it maintained the highest average R² (UCS: 0.9417, STS: 0.9329) and the lowest error metrics, confirming its robustness and generalization capability. SHAP and Pearson correlation analyses identified cement content as the primary strength determinant, while steel slag content exhibited a threshold effect, highlighting the importance of prudent gradation control in practical engineering. This study provides both a theoretical foundation and a methodological framework for analyzing variable interactions and predicting the strength development of CSSS. Full article

Phages, the most abundant entities on Earth, exhibit a complex interplay with bacteria, especially within environmental biofilms, resulting in an ecological arms race. This study investigates the interaction between phages and bacteria in the drains of beef-processing plants using high-throughput sequencing and metagenomic analysis. Metagenomic data collected from 75 drain samples from beef-processing plants were analyzed to investigate phage–bacterial interactions. First, assembled contigs were screened to identify viral sequences, which were then taxonomically annotated to determine the viral composition, including phages. Functional annotation of these viral sequences provided information about the viral genes and their roles in bacterial interactions specifically associated with attack and counterattack of bacteria. In parallel, bacterial contigs were examined to identify genes associated with antiphage defense systems, providing insights into the strategies adapted by bacteria to resist phage infection. Taxonomic annotation of viral sequences from the bulk metagenomic data revealed the presence of phages targeting Pseudomonas, Klebsiella, and Enterococcus. The higher abundance of Pseudomonas phages aligns with our previous study, where Pseudomonas was identified as the dominant bacterial genus, suggesting potential copersistence of phages and their hosts. Functional annotation of phage contigs revealed infective and lysis-related genes, highlighting their potential role in bacterial attack. Conversely, bacterial contigs encoded antiphage defense systems, including CRISPR-Cas, restriction–modification, and other defense-related genes. The study also uncovered the presence of anti-CRISPR proteins in phages, suggesting a counterattack on the bacterial defense. These findings provide evidence for phage attack, bacterial defense, and phage counterattack and may showcase the ongoing coevolutionary arms race between phages and bacteria. While this evidence looks promising, these results remain preliminary and further studies are needed to validate these findings. Still, this study provides a foundational understanding of bacteria–phage coexistence in beef-processing plant drains and paves the way for further explorations of these intricate interactions and their possible applications in controlling pathogenic microorganisms within biofilms. Full article

Natural polyphenols, particularly quercetin (QUE) and rosmarinic Acid (RA), possess significant synergistic therapeutic potential as potent antioxidants and anti-inflammatories. However, their poor stability, low water solubility, and resulting limited bioavailability severely hinder their effective clinical translation. This study addresses these fundamental limitations by designing a novel advanced drug delivery platform utilizing electrospinning. We have fabricated composite high-molecular-weight poly(L-Lactic Acid) (PLA)/polyethylene glycol (PEG) nanofibers for the simultaneous co-delivery of both QUE and RA, optimizing compound stability and release kinetics. PLA provided mechanical integrity and sustained release properties, while the incorporation of PEG strategically enhanced the mat’s wettability, enabling precise control over initial drug dissolution. Comprehensive characterization confirmed uniform, bead-free morphology and high entrapment efficiency for both polyphenols. Crucially, the PLA/PEG blend successfully achieved a biphasic release profile, featuring an initial burst release mediated by PEG followed by a sustained release phase governed by the PLA matrix. Furthermore, the performed in vitro investigations using SH-4 melanoma cells and HaCaT normal keratinocytes revealed that the prepared novel materials containing the polyphenols possessed high anticancer activity to the used cancer cell line. However, the toxicity to the normal cell line is much lower. Therefore, this novel electrospun composite scaffold offers an effective strategy to enhance the stability, control the delivery, and maximize the synergistic therapeutic benefits of quercetin and rosmarinic Acid for applications in areas such as advanced wound care, tissue regeneration, and antitumor therapies. Full article

The increasing demand for sustainable agriculture necessitates the development of eco-friendly alternatives to chemical pesticides. This study reports the design and characterization of biodegradable fibrous mats for the delivery of Bacillus subtilis, a plant-beneficial biocontrol agent, using cellulose acetate (CA) scaffolds functionalized with chitooligosaccharides (COS). Electrospun CA fibers were coated by electrospraying with COS or COS/B. subtilis suspensions in a single-step process to produce open, porous biohybrid scaffolds. Scanning electron microscopy confirmed uniform fiber formation and successful deposition of COS and bacterial layers, while ATR-FTIR spectroscopy verified the chemical composition of the fibrous mats. Water contact angle measurements indicated a shift from hydrophobic to highly hydrophilic surfaces, enhancing microbial adhesion and moisture-mediated activation. Mechanical testing demonstrated that thin COS coatings slightly improved tensile strength without compromising flexibility. Viability assays confirmed that encapsulated B. subtilis remained viable and capable of sporulation, and dual-culture assays demonstrated effective inhibition of Alternaria solani, Fusarium avenaceum, and Rhizoctonia solani. These results indicate that the electrospun/electrosprayed CA/COS platform provides a protective, sustainable, and effective delivery system for biocontrol agents. This approach offers a promising strategy for reducing reliance on synthetic pesticides while maintaining crop protection efficacy. Full article

Prostate cancer (PrCa), the second most common cancer diagnosed in men globally, remains a critical challenge in precision oncology. While PrCa can be deadly, it is highly treatable if detected early. Identifying associative factors influencing disease progression risks can help inform preliminary steps that will further the expedition of clinical therapeutic intervention decisions, which will improve treatment outcomes. While conventional PrCa progression assessment tools rely heavily on a few clinical parameters, the importance of genomic information is increasingly recognized. In this study, we evaluate the prognostic value of patients’ clinicogenomic profiles in modeling progression-free survival (PFS) of PrCa. Three survival models, namely the penalized Cox model, random survival forest, and a deep learning survival neural network, were deployed with extensive tuning applied to a dataset for a cohort of 494 patients with PrCa. This dataset, compiled from public data in The Cancer Genome Atlas (TCGA) accessed via cBioPortal, consists of relevant clinical features and single-nucleotide variant information on likely PrCa-related genes. The survival models demonstrated satisfactory discriminatory performance, with Harrell’s concordance index ranging from approximately 0.80 to 0.87 on held-out test data, indicating their ability to rank patients according to their relative progression risk among patients, while exhibiting distinct dynamics, all three models consistently identified clinical variables that indicated neoadjuvant treatment history, neoplasm cancer status, and tumor recurrence as well as the gene MYH6 as important predictor variables for PrCa PFS. Our findings suggest the incorporation of genomic data into the survival modeling workflow, thereby allowing the use of integrated clinicogenomics information to gain insights into progression risks for patients with PrCa. Full article

To address the disconnect between macro-quantity planning and micro-spatial allocation at the township level during rapid urbanization, this study developed a coupled model framework based on Multi-Objective Planning (MOP) and the Future Land-Use Simulation (FLUS) model, using Longhu Town as a case study. First, economic and ecological benefit coefficients were calibrated via the Grey Prediction Model and equivalent factor method to define three scenarios: Economic Priority (EPS), Ecological Protection (EcPS), and Balanced Development (BDS). Second, an Artificial Neural Network (ANN) was employed to quantify driving factors, coupled with self-adaptive Cellular Automata (CA) for spatial allocation in 2030. The results indicate that: (1) The model exhibits high reliability for small-scale simulation, with a Kappa coefficient of 0.95 and a Figure of Merit (FoM) of 0.29. (2) Strategic orientations lead to distinct spatial differentiation: under the EPS, urban–industrial land expands significantly northwestward (+16.60%), causing fragmented erosion of cropland; the EcPS achieves a 5.27% increase in forest land and ecological restoration through strict quantitative constraints; the BDS realizes the synergy of urban clustering and ecological enhancement with a marginal urban increase (0.72%). (3) The eastern urban sectors and northeastern cropland belts are identified as future land-use conflict hotspots. The “quantity-space” collaborative optimization path proposed in this study provides a scientific basis and dynamic simulation tool for refined territorial spatial management at the township scale. Full article

Calcium carbide slag and silica fume was used as a cement replacement material, combined with excavated soil and EPS (expanded polystyrene) particles, to develop a new green and low-carbon lightweight fluid solidified soil (LFSS). Focusing on the performance regulation of LFSS, this study adopted the paste volume ratio (PV, defined as the volume ratio of paste to total mixture) and the water–binder ratio (w/b) to systematically construct a mix ratio design system and proposed EPS particle interface modification and shell formation technology to improve the weak interface bonding between EPS and the matrix. Firstly, based on the paste volume method, the effects of PV and w/b on the flowability and strength of LFSS were analyzed, and a linear correlation model between the water–solid volume ratio and flowability, as well as a quadratic function prediction model for 28-day strength, was established. Secondly, the “core–shell structure” of EPS particles was constructed by combining EVA (ethylene-vinyl acetate) modification with the coating of calcium carbide slag–silica fume paste. Considering the influence of the coating method, w/b, and material mass ratio on interface bonding comprehensively, the optimal process parameters were determined to achieve the interface reinforcement of EPS particle. The results showed that the water–solid volume ratio was significantly linearly correlated with the flowability of LFSS. PV and w/b respectively controlled the framework formation and pore structure evolution of LFSS, with optimal overall performance at PV = 0.55 and w/b = 2.5. The modification shell formation significantly reduced the shell loss rate of EPS particles and increased the 28-day compressive strength of LFSS by 21.7%. SEM (scanning electron microscope) and EDS (energy-dispersive spectroscopy) analysis further revealed that the shell-formation technique promoted the densification of the interface transition zone, enhanced the deposition of hydration products, and strengthened the synergistic effect of Na and Ca elements, thereby significantly improving interface bonding and overall structural stability. This study established a “mix ratio optimization-modification and shell formation” dual-regulation mechanism, providing an effective technical approach and theoretical basis for the engineering application of calcium carbide slag–silica fume-based LFSS. Full article

Waste oyster shell powder (OP) and calcined oyster shell powder (COP) were used as bio-fillers in asphalt mastics. Limestone powder (LP) served as the control. This study employed rheological theory to quantify filler–asphalt interactions. Dynamic shear rheometry (DSR), Black diagrams, and master curves were analyzed to determine critical volume fraction (φ_crit), interaction parameter (C), and complex viscosity increment (∆η*). Results indicate that OP mastics exhibit the lowest φ_crit (0.510) and highest C value (1.133), demonstrating the strongest interfacial interaction. COP shows intermediate interaction strength (φ_crit = 0.542), yet both OP and COP outperform LP (φ_crit = 0.617) in high-temperature deformation resistance within the 0.23–0.53 filler volume fraction range, evidenced by superior complex shear modulus (G*) master curves and pronounced ∆η* increases. Grey relational analysis identifies specific surface area and CaCO₃ content as governing factors. Optical microscopy and FTIR confirm that filler–asphalt interactions are dominated by physical adsorption without chemical bond formation. These findings elucidate the performance advantages of both raw and calcined oyster shell powders and provide a theoretical basis for their application as sustainable high-performance bio-fillers in asphalt pavements. Full article

Background: Breast cancer remains a major health issue, with bone metastases negatively impacting patient outcomes. The biochemical and biological functions of the exon 4-splice isoform (ZNF217-ΔE4) of the oncogenic transcription factor ZNF217 have been poorly investigated. Methods/Results: This study, for the first time, elucidates through advanced live-cell single-molecule tracking microscopy that the C-terminus of ZNF217 influences chromatin engagement and binding stability. ZNF217-ΔE4 retains its ability to be recruited and to promote positive transcriptional activity. CRISPR/Cas9-mediated silencing of the ZNF217 gene in MDA-MB-231 breast cancer cells impairs cell aggressiveness, while reintroduction of the ZNF217-ΔE4 isoform is sufficient to restore increased cell proliferation, migration, invasion, and stemness features. In vivo, ZNF217 ΔE4—although less potent than the wild-type isoform—accelerates the formation of bone marrow micrometastases. A retrospective analysis of primary breast tumors revealed that patients with high ZNF217-ΔE4 mRNA levels had a higher risk of developing bone metastases. Conclusions: Overall, this study identifies ZNF217-ΔE4 as a novel functional isoform that mediates breast cancer cell aggressiveness and bone marrow homing. It also highlights this isoform as a promising biomarker and potential therapeutic target for breast cancers at elevated risk of bone metastasis. Full article

Elateridae (Coleoptera: Elateroidea) are renowned for their clicking mechanism. However, several lineages exhibit body softening that compromises this mechanism, particularly within Plastocerini, Drilini, and Omalisinae. It remains unclear how this body softening is anatomically achieved and which specific structures are degraded in relation to the loss of clicking function. To elucidate the internal morphological adaptations and distinguish them from hard-bodied clicking elateroids, we employed micro-CT to scan Plastocerus thoracicus and reconstruct its thoracic morphology in 3D and quantified key muscle ratios (e.g., M2/M60, M4/M60). Based on our study of P. thoracicus, a detailed comparison was made with previously reported data on Campsosternus auratus (Elateridae) and Cerophytum lii (Cerophytidae). Three-dimensional reconstructions revealed significant structural divergences in P. thoracicus: (1) the clicking-related muscles M4 are markedly weaker than those in Ca. auratus and Ce. Lii. (2) the prosternal process (PP) is extremely narrow. The posterior part of the pronotum exhibits underdeveloped regions, including the posterodorsal evagination (PdE) and the posteromedial process (PmPr). (3) the mesonotum (i.e., the “biological spring” identified in previous studies) is greatly flattened and weakened. (4) the flight muscles (M60, M64) and walking muscles (M74, M75) exhibited significantly bigger volume than Ca. auratus and Ce. lii. These findings provide critical data for understanding the morphological evolution of Elateridae and offer insights into the functional adaptations of the clicking mechanism through comparative anatomy. 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

Metadata extraction from natural history collection labels is a pivotal task for the online publication of digitized specimens. However, given the scale of these collections—which are estimated to host more than 2 billion specimens worldwide, including ca. 400 million herbarium specimens—manual metadata extraction is an extremely time-consuming task. Thus, automated data extraction from digital images of specimens and their labels therefore is a promising application of state-of-the-art computer vision techniques. Extracting information from herbarium specimen labels normally involves three main steps: text segmentation, multilingual and handwriting recognition, and data parsing. The primary bottleneck in this workflow lies in the limitations of Optical Character Recognition (OCR) systems. This study explores how the general knowledge embedded in multimodal Transformer models can be transferred to the specific task of herbarium specimen label digitization. The final goal is to develop an easy-to-use, end-to-end solution to mitigate the limitations of classic OCR approaches while offering greater flexibility to adapt to different label formats. Donut-base, a pre-trained visual document understanding (VDU) transformer, was the base model selected for fine-tuning. A dataset from the University of Pisa served as a test bed. The initial attempt achieved an accuracy of 85%, measured using the Tree Edit Distance (TED), demonstrating the feasibility of fine-tuning for this task. Cases with low accuracies were also investigated to identify limitations of the approach. In particular, specimens with multiple labels, especially if combining handwritten and typewritten text, proved to be the most challenging. Strategies aimed at addressing these weaknesses are discussed. Full article

Understanding the impact of monsoonal oscillations during past climatic changes in the Arabian Sea is crucial for improving climate model predictions under ongoing global warming. This study investigates whether millennial-scale climate shifts in Greenland, specifically Dansgaard–Oeschger events 12–11, affected the Indian Ocean monsoon system and the associated productivity and oxygen minimum zone (OMZ) dynamics in the northwestern Arabian Sea. In the Arabian Sea, DO stadials correspond to reduced water-surface productivity, well-ventilated intermediate water masses, and a weakened or absent OMZ. Contrarily, DO interstadials are distinguished by enhanced water-surface productivity, a reorganization of intermediate water masses, and a reinvigoration of the OMZ. Eleven sediment samples from ODP Site 721A were analyzed using a multiproxy approach combining total organic carbon, C/N ratios, bulk-sediment isotopes (δ¹⁵N, δ¹³C), and the relative abundances of Globigerina bulloides and Globigerinoides ruber, complemented by isotopic data (δ¹³C, δ¹⁸O) from G. ruber shells. Further Mg/Ca–δ¹⁸O and δ¹⁸O_sw measurements were included to refine the reconstruction of surface-water hydrography linked to productivity changes. Results reveal significant oscillations in water-surface productivity and OMZ intensity, modulated by shifts in monsoon strength and water-column ventilation. Enriched δ¹⁵N values, elevated TOC, and increased G. bulloides relative abundances reflect intensified denitrification and organic matter preservation under a stronger southwest monsoon, whereas depleted δ¹⁵N, reduced TOC, and higher G. ruber abundance indicate enhanced ventilation and a weaker OMZ under northeast monsoon dominance. These findings provide new evidence that refines the paleoceanographic history of the Arabian Sea. Additionally, they demonstrate that high-latitude climatic forcing during DO events modulated Arabian Sea monsoon dynamics and oxygenation through strong interhemispheric teleconnections. Full article

With increasing life expectancy, a growing proportion of patients undergoing surgery for gynecologic cancers are older adults, underscoring the need for reliable predictors of postoperative recovery and patient engagement. Cognitive function and physical frailty are recognized determinants of surgical outcomes, yet their relative impact on patient centered outcomes remains insufficiently explored. This prospective observational study included 68 women aged 65 years and older who underwent abdominal surgery for gynecologic malignancies. Preoperative cognitive function was assessed using the Montreal Cognitive Assessment, and physical frailty was evaluated with the Clinical Frailty Scale. Postoperative outcomes included early recovery parameters, complications, surgical decision satisfaction, and home-based adherence. Higher cognitive scores were associated with earlier mobilization, shorter hospital stay, better postoperative adherence, and greater decision satisfaction, whereas higher frailty scores were associated with delayed recovery and increased complication risk. In regression analyses, preoperative cognitive function was significantly associated with both postoperative adherence and surgical decision satisfaction, whereas physical frailty was not. These findings indicate that preoperative cognitive screening may have predictive value for patient centered recovery behaviors and decision satisfaction in this setting; however, the prediction estimates should be considered exploratory and warrant validation in larger, multicenter cohorts. Full article