Search Results (29,875)

Background/Objectives: Triple-negative breast cancer remains a major therapeutic challenge due to its aggressive behavior and limited treatment options. Methods: In this study, an integrated multi-omics strategy combining SILAC-based quantitative proteomics, shotgun lipidomics, and targeted metabolomics was applied to characterize the biomolecular response of MDA-MB-231 cells following exposure to the Ag@MSN-Tf-SeNPs nanosystem. Results and Conclusions: The complementary analytical platforms provided a comprehensive and system-level view of the cytotoxic effects induced by the nanosystem, highlighting its potential as an antitumoral nanotherapeutic approach. Exposure resulted in reduced cell growth and metastatic potential, associated with DNA damage-induced cell-cycle arrest, disruption of protein biosynthesis, and impaired protein quality control linked to Ca²⁺ homeostasis imbalance. In addition, significant alterations in lipid metabolism were observed, including disruption of cholesterol biosynthesis. These changes, together with disturbances in glycolysis and the tricarboxylic acid cycle, and alterations in NAD⁺/NADH balance, indicate the induction of oxidative stress driven by reactive oxygen species accumulation. Furthermore, the integration of multi-omics data revealed the activation of compensatory mechanisms aimed at restoring cellular homeostasis, including metabolic rewiring and stress-response pathways, although these responses were insufficient to counteract nanosystem-induced cytotoxicity. Full article

Firms in traditional manufacturing clusters face lock-in situations when crises disrupt established routines. The study analyzes how firms embedded in a mature industrial cluster responded to COVID-19, focusing on location, firm, and relation-based indicators in the Denizli textile district in Türkiye, which remains under-represented in resilience research. A mixed-methods analysis was conducted using primary and secondary data. With secondary data, the textile industry was determined as the mature industrial cluster in Denizli by conducting a three-star analysis (which was used as the cluster analysis method for showing mature, potential, and candidate clusters) within the region’s manufacturing industries. By using primary data with a purposive sampling approach, a logistic regression model is employed to analyze a survey administered to 118 textile firms. It is found that, even though locating in a specialized cluster, partnering with NGOs, and product diversification contribute positively to resilience in adapting to crises, no new growth path is created by firms either locating in the specialized cluster or in other parts of the city. Due to the cognitive and political lock-in and power of local institutional production systems in the textile industry in Türkiye, our case conforms more to the engineering type of resilience to crises than to the adaptive type. Full article

Improving farmland conditions suitable for agricultural machinery is important for enhancing agricultural production resilience. Farmland consolidation suitable for agricultural machinery (FCAM) is regarded as an effective means. Using panel data from 330 Chinese cities from 2013 to 2023, this study evaluated the potential of FCAM and agricultural production resilience. The potential of FCAM was defined as the broader suitability of farmland for mechanized operations rather than the direct intensity of implemented FCAM policies. Their spatial association and quantitative relationship were then examined. The results showed that the potential of FCAM and agricultural production resilience both increased during the study period, with growth rates of 2.61% and 3.13%, respectively, and both followed a two-stage growth pattern. Spatially, high values were mainly concentrated in the Northeast China Plain, while low values were found in the Southwest mountainous region, showing a clear northeast–southwest gradient. Bivariate spatial correlation analyses indicated a significant, increasing spatial association between the potential of FCAM and agricultural production resilience, suggesting that farmland geographical endowments strongly shape their spatial distributions. Regression results further showed that the potential of FCAM is positively associated with agricultural production resilience, indicating that improving mechanization suitability can enhance the robustness, adaptability, and transformability of agricultural production systems. The estimated inverted U-shaped relationship further indicates diminishing marginal returns at higher potential of FCAM, while most regions remained below the turning point during the study period. These findings provide evidence for regionally differentiated and resilience-oriented FCAM schemes. Full article

Alternanthera philoxeroides, an invasive alien species, spreads rapidly in river systems via vegetative propagation from stem fragments, requiring river-system-scale monitoring to understand its expansion dynamics and habitat preferences. This study used multi-temporal Sentinel-2 data to analyze spatio-temporal variations in fractional vegetation cover (FVC) within a 3.5 km river reach. FVC estimates derived from vegetation indices were validated against high-resolution aerial images, with an EVI-based model achieving the highest accuracy (RMSE = 9.2%), enabling reliable monitoring even in narrow (~24 m) channels. Time-series analysis from 2019 to 2024 revealed downstream expansion beginning in 2022. Annual maximum FVC (C_max) was used to assess relationships with removal records and bank structures, showing that removal effects were temporary and more pronounced in the first year, while steel sheet-pile banks limited vegetation growth compared to concrete revetments. These results demonstrate that Sentinel-2 data can provide an effective and accessible tool for evaluating invasive plant dynamics and management effectiveness in low-flow river systems where A. philoxeroides dominates the floating vegetation community. Full article

Based on quantum chemical theory, the gas-phase chemical cross-reaction pathways in metal–organic chemical vapor deposition of InAlN films have been investigated. First, calculations of the oligomerization reactions of Al and In amides were performed to investigate the relative difficulty of generating several dimers and trimers within this system. The elimination reaction pathways were then investigated. The final stable products of the polymers were analyzed from both thermodynamic and kinetic perspectives, and the propensities of the reaction pathways were assessed from the viewpoint of the reaction rates. The results indicated that in the gas-phase reaction pathways of InAlN grown by metal–organic chemical vapor deposition, the equilibrium temperature for the dimerization reactions lies between 960 and 1061 K, and above this temperature range, dimers cannot form. Trimer formation is unlikely during the InAlN growth process. At higher reaction temperatures, the oligomers tend to first undergo intramolecular elimination, losing two CH4 molecules to form intermediate products, which then react with NH3 via intermolecular elimination to yield stable products. At lower reaction temperatures, the tendency is for continuous intermolecular elimination with NH4 to generate stable, methyl-free products. Full article

Reliable estimation of winter wheat yield is critical to food system stability and farmland management. Integrating multi-spectral remote sensing data with agronomic parameters represents a primary strategy for improving yield estimation accuracy. However, existing research often overlooks parameters reflecting crop population structure and fails to account for dynamic shifts in the contributions of multidimensional agronomic variables across growth stages, thereby limiting prediction accuracy and model stability. To address these limitations, a winter wheat yield estimation model was developed. This model integrates multi-source and multi-temporal data, incorporates stem tiller density, a key population structure parameter, and accounts for dynamic variation across growth stages. Unmanned aerial vehicle multi-spectral images were collected at four key growth stages: jointing (stem elongation with detectable nodes), booting (flag leaf sheath swelling preceding heading), heading (spike emergence) and filling (grain filling with dry matter accumulation). Three growth indicators, stem tiller density, leaf area index and above-ground biomass, were measured. Two comprehensive growth indicators were derived using the coefficient of variation and the CRITIC weighting methods (CGI_CR). Correlation and feature importance analyses were used to identify sensitive vegetation indices (VIs), which were subsequently integrated with the comprehensive growth indicators. Single-stage, multi-source feature fusion and multi-temporal yield estimation models were established using the Kernel Extreme Learning Machine and its optimised algorithm using the Crested Porcupine Optimizer. The results showed the following: (1) among the individual growth stages, features from the filling stage achieved the highest prediction accuracy; (2) the fusion of multi-source features (VIs + CGI_CR) enhanced the prediction accuracy of the model, achieving a validation set R² of 0.884 and a relative prediction deviation of 2.916 at the filling stage; and (3) the multi-temporal model further improved predictive performance, with the validation R² reaching 0.920, indicating that information from different growth stages contributed complementarily to yield prediction and improved overall model performance. By contrast, the model exhibited relatively weak predictive capability at the early growth stages and was better-suited to early risk identification. Meanwhile, its generalisation ability under cross-regional and inter-annual conditions still requires further validation. Overall, integrating multi-source and multi-temporal data can enhance the precision and stability of predicting winter wheat yield, thereby facilitating precision agriculture management. Full article

Global angel investment and venture capital are key financial drivers supporting the long-term growth of technology companies, and they play a vital role in improving the global science and technology innovation financial system and advancing green and sustainable transformation. This paper uses data on technology-sector companies listed on the A-share market from 2017 to 2025 to construct a multi-period DID model. It empirically examines the impact of angel investment and venture capital on the sustainable development of technology companies and investigates the moderating effect of ESG performance. The study finds that angel investment can significantly enhance the level of sustainable development in technology firms. Mechanism tests indicate that angel investment indirectly empowers sustainable development by attracting and introducing venture capital. The moderating effect shows that strong ESG performance positively reinforces the promotional role of angel investment and venture capital in the sustainable development of technology firms. Heterogeneity analysis reveals that these enhancement and moderating effects are more pronounced in high-tech industries, private enterprises, and asset-light technology firms. These findings provide empirical evidence and policy guidance for governments worldwide to direct venture capital toward supporting science and technology enterprises, help technology firms improve their ESG governance systems, and achieve long-term sustainable operations. Full article

Background/Objectives: Sacituzumab govitecan (SG, IMMU-132) is a TROP2-directed antibody–drug conjugate carrying SN-38. Patients with colorectal liver metastasis (CRLM) still have limited treatment options after first-line systemic therapy, and the preclinical pharmacological value of TROP2-directed SN-38 delivery in CRLM remains insufficiently defined. Methods: Public single-cell RNA-sequencing data were reanalyzed to explore the distribution of TACSTD2/TROP2-positive epithelial-associated cells in adjacent normal tissues, primary colorectal cancer, and CRLM. The prognostic relevance of TACSTD2 was evaluated using the Kaplan–Meier Plotter database. TROP2-knockdown and TROP2-overexpressing colorectal cancer models were used to assess IMMU-132 response in vitro and in vivo. Pharmacological antitumor activity was further evaluated using subcutaneous xenografts, syngeneic intrasplenic liver metastasis models, and CRLM patient-derived organoids (PDOs). Transcriptomic profiling and γ-H2AX immunofluorescence were used to explore treatment-associated molecular changes. Results: At the patient/sample level, TACSTD2/TROP2-positive epithelial-associated cells showed numerically higher proportions in primary colorectal tumors and liver metastases than in adjacent normal tissues, and high TACSTD2 expression was associated with inferior overall survival in a public survival database. TROP2 knockdown attenuated IMMU-132-induced growth inhibition, apoptosis, and suppression of colony formation. In vivo, IMMU-132 suppressed colorectal tumor growth and reduced liver metastatic burden, with more evident activity in human TROP2-overexpressing models. In a limited exploratory CRLM PDO cohort established after first-line therapy, liver metastasis-derived PDOs showed lower normalized AUC values than primary tumor-derived PDOs. Transcriptomic analysis and representative γ-H2AX immunofluorescence suggested that IMMU-132 treatment was associated with changes in adhesion/cytoskeletal-related pathways, Wnt/cancer-associated transcriptional programs, and DNA damage-associated signals. Conclusions: These in vitro, in vivo, and PDO-based findings support further preclinical pharmacological evaluation of TROP2-directed SN-38 delivery by IMMU-132 in biomarker-annotated CRLM models, particularly in the post-first-line systemic therapy setting. Full article

With the rapid expansion of intensive aquaculture, the frequent outbreak of diseases and the overuse of antibiotics have become increasingly critical issues. Therefore, developing green and efficient antibiotic alternatives is essential for the sustainable growth of the industry. As a novel probiotic, Bacillus velezensis has shown great potential in improving the disease resistance of aquatic animals, owing to its excellent spore-forming ability, broad-spectrum antibacterial activity, and immunoregulatory functions. This paper systematically reviews the main mechanisms by which B. velezensis enhances disease resistance in aquatic animals, including directly inhibiting pathogens through the secretion of various lipopeptides and polyketides such as surfactin, iturin, and fengycin; interfering with pathogen quorum sensing systems via quorum quenching enzymes, thereby suppressing virulence factor expression and biofilm formation; modulating intestinal microbiota structure to increase the abundance of beneficial bacteria while reducing pathogenic proliferation; and activating the non-specific immune system of the host to upregulate immune-related indicators such as acid phosphatase, superoxide dismutase, and key cytokines (such as IL-1β, TNF-α). In addition, this review summarizes the application effects of B. velezensis on improving aquaculture water quality and promoting host growth. Furthermore, the potential ecological impacts on natural microbial communities and strain-dependent biosafety risks are evaluated. Finally, current research limitations—such as strain-specific functional differences, insufficient in-depth analysis of mechanisms, and inconsistent application outcomes—are discussed. Future prospects for promoting the efficient and stable application of B. velezensis in aquaculture through strategies including gene editing, multi-omics integration, and precise formulation compounding are also proposed. Full article

Chromium (Cr) contamination poses a serious threat to agricultural productivity and food safety, yet effective strategies for mitigating Cr toxicity under practical cultivation conditions remain limited. In this study, green-synthesized selenium nanoparticles (SeNPs), prepared from banana peel extract (average particle size: 112.9 nm), were evaluated against conventional sodium selenite (Na₂SeO₃) for alleviating Cr(VI) toxicity in Ipomoea aquatica Forssk. grown in a dynamic cyclic hydroponic system. Plants were exposed to 20 mg L⁻¹ Cr(VI) and treated with SeNPs or Na₂SeO₃ at 1 and 10 mg L⁻¹, respectively, for a duration of one week. Green-synthesized SeNPs exhibited excellent colloidal stability (zeta potential: −35.5 mV) and an amorphous spherical morphology. Relative to the Cr-only treatment, 10 mg L⁻¹ SeNPs almost completely restored plant biomass and root growth, decreased shoot Cr accumulation by 62.2%, and recovered total chlorophyll content to 94.8% of the control level. By comparison, 10 mg L⁻¹ Na₂SeO₃ restored total chlorophyll to 74.2% of the control and reduced shoot Cr accumulation by 50.6%. SeNPs also elicited a stronger antioxidant response, markedly increasing SOD, POD, and CAT activities while significantly lowering H₂O₂, MDA, and proline levels, demonstrating a greater capacity than selenite to alleviate Cr-induced oxidative damage. SeNPs also restored the uptake of essential mineral nutrients (N, P, K, Ca, and Mg), improved soluble sugar and protein contents, and promoted selenium biofortification in edible shoots. Although both selenium forms alleviated Cr-induced growth inhibition and oxidative damage, SeNPs consistently outperformed Na₂SeO₃ owing to their higher bioavailability and sustained physiological activity. Overall, this study demonstrates that green-synthesized SeNPs provide an efficient and sustainable strategy for reducing Cr accumulation while simultaneously improving crop growth, antioxidant capacity, and nutritional quality under agriculturally relevant hydroponic conditions, highlighting their potential for safer food production and agricultural waste valorization. Full article

The transition toward reusable food packaging driven by European circular economy regulations introduces new food safety challenges related to microbial persistence and cross-contamination. GS-2 is a novel, food-safe antimicrobial formulation developed for use as a coating on reusable packaging materials. In the present study, the intrinsic antimicrobial activity of GS-2 was evaluated in liquid suspension against foodborne bacterial (Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella enterica Agona) and fungal pathogens (Aspergillus flavus and Aspergillus niger), and the transcriptomic response of L. monocytogenes following sublethal GS-2 exposure was investigated. GS-2 exhibited concentration-dependent microbicidal activity, with strong reductions observed at ≥2.8–3.0% against bacterial strains and A. flavus, while A. niger demonstrated resistance. Among bacteria, L. monocytogenes showed the greatest sensitivity, with populations reduced below detection limits at 3% GS-2. To elucidate mechanistic responses, RNA sequencing was performed on L. monocytogenes exposed to sublethal GS-2 concentrations (0.1–1.0%). Transcriptomic analyses using discrete and continuous models revealed a pronounced adaptive stress response at 0.5% GS-2, characterized by coordinated upregulation of pathways involved in carbon, nitrogen, and nucleotide metabolism. At higher sublethal concentrations (1%), transcriptional profiles shifted toward growth arrest and cellular damage management. These findings support GS-2 as a promising antimicrobial for enhancing the microbial safety of reusable food packaging systems. Full article

Eucalyptus is an important timber species characterized by strong adaptability and rapid growth. However, adverse environmental conditions such as drought stress severely impact its growth and productivity. Arbuscular mycorrhizal (AM) fungi form beneficial symbiotic relationships with Eucalyptus root systems and significantly enhance plant stress tolerance. In this study, we identified 111 WRKY genes in Eucalyptus grandis and systematically characterized their physicochemical properties, phylogenetic relationships, gene structures, conserved motifs, synteny, and cis-acting elements. Notably, AM fungal symbiosis significantly enhanced the biomass, plant height, and root length of E. grandis seedlings under drought stress. Through integrated RNA-seq and qRT-PCR analyses, we identified 12 EgWRKY genes that responded to drought stress during AM fungal symbiosis, with their expression levels significantly elevated in AM-inoculated roots under drought conditions. These findings provide novel insights into the regulatory roles of EgWRKY genes in AM-mediated drought tolerance and establish a foundation for understanding the molecular mechanisms underlying WRKY-mediated stress responses in E. grandis. Full article

Iodine is an essential micronutrient required for coordinating thyroid hormone synthesis, growth, neurodevelopment, metabolism, and immune function across humans and domesticated mammals. Molecular iodine can act as an antioxidant, anti-inflammatory, and anti-proliferative agent in several tissues, but these mechanistic effects require confirmation in well-designed human studies. Recommended intakes fall within a narrow optimal range, reflecting a U-shaped response curve in which adequate intake supports systemic homeostasis, while both deficient and excessive intakes can impact immune function. Chronic deficiency impairs neurodevelopment and reproductive performance and weakens the host microbial defences, while sustained excess promotes oxidative stress, alters cytokine profiles, and in genetically susceptible individuals, increases the risk of subclinical or overt thyroid dysfunction and autoimmune thyroid disease. This review summarizes iodine nutrikinetics, dose-dependent outcomes and susceptibility in humans and domesticated mammalian species, emphasizing the importance of maintaining appropriate iodine status to support immunocompetence while minimizing adverse effects. Full article

Hepatic fibrosis is a pathological process involving the systemic reconfiguration of the liver microenvironment under chronic liver injury. It is a pathological wound healing response characterized by the excessive deposition of extracellular matrix (ECM) driven by the activation of hepatic stellate cells (HSCs), starting with the capillarization of liver sinusoidal endothelial cells (LSECs). This process can lead to liver structure destruction, portal hypertension, and even liver dysfunction, and is a major driving factor for death related to liver diseases. During this process, hypoxia initiates the transcriptional upregulation of effector molecules such as vascular endothelial growth factor (VEGF) and Lysyl oxidase (LOX) by stabilizing hypoxia-inducible factors (HIFs), inducing changes in LSEC phenotype and activation of HSCs, thus becoming a core driving factor. Activated HSCs not only exacerbate the capillarization of LSECs and tissue hypoxia but also strengthen the transcriptional activity of HIFs through autocrine/paracrine signaling, establishing a positive feedback loop linking hypoxia to HIFs and HSC activation, continuously driving the progression of liver fibrosis and significantly increasing the probability of chronic liver diseases evolving into cirrhosis and the risk of death. This review will analyze the mechanism of liver fibrosis driven by hypoxia, integrate the current treatment landscape, focus on exploring the therapeutic targets related to hypoxia-induced activation of hepatic stellate cells leading to liver fibrosis, and evaluate their translational potential. It is expected to provide information for future effective anti-fibrotic intervention strategies. Full article

The discovery of activating epidermal growth factor receptor (EGFR) mutations transformed the management of non-small cell lung cancer and has driven two decades of therapeutic advances in precision oncology across metastatic, resectable, and unresectable locally advanced disease, including central nervous system (CNS) control. Consequently, treatment outcomes for patients with tumors harboring classical EGFR mutations have markedly improved. Despite these advances, many questions remain unanswered, and the expanding number of treatment options has created new challenges in treatment selection and sequencing. This narrative review summarizes contemporary data on the management of classical EGFR-mutant NSCLC, encompassing novel therapeutic approaches across disease stages, biomarker-informed resistance strategies, multimodality treatment integrating radiotherapy, CNS-directed management, and challenging scenarios such as small-cell transformation. We also discuss emerging fourth-generation inhibitors, nucleic-acid delivery platforms, and data-enabled personalized treatment. We highlight evolving standards of care, unresolved knowledge gaps, and research priorities for the next decade. Full article