Search Results (9,972)

Multicomponent mixed lanthanide oxide (MMLO) nanoparticles possess considerable potential as multimodal imaging agents because they integrate diverse excellent optical and magnetic properties within a single nanoparticle. Herein, we present triply and quadruply mixed lanthanide oxide nanoparticles, namely, gadolinium (Gd)/dysprosium (Dy)/europium (Eu) oxide (GDEO), Gd/Dy/terbium (Tb) oxide (GDTO), and Gd/Dy/Eu/Tb oxide (GDETO) nanoparticles. Gd³⁺ can strongly induce positive (T₁) contrast in magnetic resonance imaging (MRI), Dy³⁺ and Tb³⁺ can generate negative (T₂) contrast in MRI, and Eu³⁺ and Tb³⁺ emit visible photons that are applicable to fluorescence imaging (FI). All the nanoparticles were grafted with hydrophilic, biocompatible polyacrylic acid (PAA) to enhance colloidal stability and biocompatibility and further grafted with small amounts of an organic photosensitizer, 2,6-pyridinedicarboxylic acid (PDA), to obtain a high absolute fluorescent quantum yield (QY) with an extended fluorescent lifetime (τ). All PAA-MMLO and PAA/PDA-MMLO nanoparticles exhibited nearly monodispersed particle-size distributions with average particle diameters of ~2 nm and displayed considerably higher longitudinal (r₁) and transverse (r₂) water proton spin relaxivities than commercial molecular MRI contrast agents. The PAA/PDA-GDEO, PAA/PDA-GDTO, and PAA/PDA-GDETO nanoparticles exhibited high absolute QYs of 45, 29, and 61%, respectively, and long τ values of 1–2 ms, making them suitable for time-delayed noise-free fluorescence signal detection. These findings confirm the high potential of PAA-MMLO nanoparticles as T₁ and/or T₂ MRI contrast agents and PAA/PDA-MMLO nanoparticles as both T₁ and/or T₂ MRI and FI agents. Full article

Pear black spot disease is a serious fungal disease during pear production; salicylic acid is a core signaling molecule that regulates the expression of plant disease resistance genes. To elucidate the intrinsic association between salicylic acid-induced resistance to pear black spot disease and lignin biosynthesis, in vitro plantlets of two pear cultivars, ‘Xinli No.7’ and ‘Xueqing’, were employed as experimental materials. After 60 h SA pretreatment, the leaves were inoculated with the pathogen Alternaria alternata. Leaf samples were harvested at 0, 8, 16, 24, and 48 h post-inoculation to determine phenylalanine ammonia-lyase activity, quantify lignin content, and analyze the transcript levels of genes involved in lignin synthesis. The results demonstrated that, relative to the untreated control group, SA treatment significantly enhanced phenylalanine ammonia-lyase activity and promoted lignin accumulation in both ‘Xinli No.7’ and ‘Xueqing’. Moreover, multiple key genes associated with lignin biosynthesis—including PbrPAL1, Pbr4CL1, PbrCOMT, PbrCCoAOMT, PbrCAD, and PbrPOD—were markedly upregulated, with their expression levels increasing by 3.5–15 fold. Transcript profiles of PbrHCT1, PbrHCT4, and PbrC3H1 exhibited cultivar-specific divergence between the two varieties. Notably, the susceptible cultivar ‘Xueqing’ displayed a distinct lag phase and attenuated response in the expression of all lignin-related genes compared with the other cultivar. This study provides reference for green prevention and sustainable development of pear. Full article

Background and Objectives: Aggressive cancer development is characterized by rapid tumor growth and progressive immune dysfunction. Tumor-derived microRNAs (miRNAs) emerge as master regulators of both malignant transformation and immune evasion, making them promising therapeutic targets. Using the highly aggressive CT-26 peritoneal adenomatosis model, this study explored the potential of selective miRNA inhibition to simultaneously suppress tumor growth and overcome immunosuppression. Methods and Results: Our results revealed that inhibition of miR-155, miR-21, and miR-17 by methylsulfonyl phosphoramidate (mesyl) oligonucleotides exhibited markedly different therapeutic profiles. miR-155 inhibition demonstrated minimal efficacy. miR-21 suppression provided early tumor regression and prevented cancer-associated thymic atrophy, translating into extended survival. miR-17 inhibition displayed delayed but superior tumor growth inhibition, significantly reducing pathologically elevated polymorphonuclear myeloid-derived suppressor cell (MDSC) populations, and nearly doubled animal lifespan. Combination therapy targeting all three miRNAs integrated these complementary mechanisms, maintaining consistent anti-tumor efficacy across early and late stages while providing thymic protection and MDSC reduction. Importantly, therapeutic responses in vivo substantially exceeded predictions based on in vitro tumor cell proliferation and motility measurements, revealing critical contributions of systemic immunomodulation. Conclusions: These findings demonstrate that miRNA inhibition reshapes tumor–immune interactions, positioning anti-miRNA therapeutics as immunomodulatory agents for effective colorectal cancer treatment. Full article

Background: Triple-negative breast cancer (TNBC) is more likely to metastasise to the lungs than other breast cancer (BrCa) types, yet the molecular interactions within the tumour microenvironment (TME) at secondary sites remain poorly understood. Methods: This pilot study aimed to explore the metabolic crosstalk between MDA-MB-231 TNBC cells and MRC-5 lung fibroblasts within a co-culture system to replicate the lung metastatic TME. Co-cultures were also treated with Vitamin D or Vitamin E to evaluate the effects of these nutraceuticals on the metabolic crosstalk between TNBC cells and fibroblasts. Results: Our findings demonstrate that co-culture induced the activation of fibroblasts into cancer-associated fibroblasts (CAFs), evidenced by increased α-SMA and FAP expression. Metabolic profiling revealed that TNBC cells in co-culture displayed increased expression of enzymes associated with oxidative phosphorylation (OXPHOS) and glutamine metabolism, while fibroblasts exhibited a metabolic profile consistent with glycolysis and lactate metabolism. Vitamin D inhibited lactate metabolism and HIF-1α expression in fibroblasts while suppressing TCA cycle activity in cancer cells, suggesting a potential role in disrupting oncogenic metabolic crosstalk. Conversely, Vitamin E treatment was associated with increased expression of TCA cycle and oxidative metabolism-related markers in BrCa cells without significantly affecting fibroblast glycolysis. Such differential metabolic responses may contribute to metabolic heterogeneity within the tumour microenvironment. Conclusions: These results provide valuable insights into the metabolic dynamics of TNBC metastases in the lung TME and demonstrate that Vitamins D and E exert distinct effects on metabolic crosstalk between cancer cells and fibroblasts. These findings may have significant implications for the potential supplementation of Vitamins D and E in patients with metastatic TNBC and justify further in-depth analysis. Full article

Background: Drought stress is a primary environmental constraint limiting crop growth and productivity. Current drought-related plant research predominantly focuses on whole-leaf analyses, neglecting the spatial heterogeneity of metabolites within leaf tissues. Methods: This study combined transcriptomic and metabolomic approaches to investigate spatially distinct metabolic responses in marginal versus central regions of Medicago lupulina L. leaves under PEG-simulated drought. Results: Findings demonstrated that TCA cycle metabolites exhibited relative stability between leaf margins and centers under drought conditions, suggesting preserved core metabolic functionality in central tissues to sustain stress tolerance. Additionally, shikimic acid displayed a significantly reduced regional gradient in stressed tissues (PEG Margin vs. PEG Center) compared to controls. Phenylalanine, tryptophan, liquiritigenin, isoliquiritigenin, coproporphyrin III, and coproporphyrinogen III itself exhibited significantly increased internal gradient differences in stressed groups compared to control groups. The coordinated upregulation of key biosynthetic genes (e.g., TAT, AST, FNS II) in both the marginal and central regions of stressed leaves indicates a metabolic shift toward the biosynthesis of downstream defensive flavonoids. These metabolites and genes accumulated preferentially in margin regions of stressed leaves, indicative of localized activation of defense-associated metabolic pathways. Conclusions: This study reveals a spatially partitioned metabolic response to drought stress in M. lupulina leaves, where defensive metabolism is preferentially enhanced at the leaf margins while core metabolic homeostasis is maintained. These findings provide new spatial insights into plant drought acclimation and identify potential targets for improving crop resilience through the fine-tuning of local metabolism. Full article

Terpenes are major determinants of tea aroma, and terpene synthases (TPSs) catalyze key steps in terpenoid biosynthesis. To capture gene-family variation beyond a single reference, we performed a pan-genome–based analysis of TPS genes across nine Camellia genomes (three wild tea relatives and six cultivated Camellia sinensis accessions) and integrated pan-transcriptome profiling across eight tissues. We identified 381 TPS genes; wild species contained more TPSs than cultivated accessions (mean 58.3 vs. 34.3), suggesting a putative contraction. Phylogenetic analysis with Arabidopsis TPSs classified Camellia TPSs into five subfamilies, dominated by TPS-b (149) and TPS-a (140), whereas TPS-c was rare (8). Gene-structure and physicochemical analyses revealed marked subfamily divergence, with TPS-c showing highly conserved coding-region length. Orthology clustering assigned 355 TPSs to 19 orthogroups, including five core groups (190 genes, 53.5%) and 14 dispensable groups (165 genes, 46.5%); core/non-core status was significantly associated with subfamily composition. Tandem and proximal duplication contributed most to TPS expansion (29.4% and 29.1%), and all orthogroups exhibited copy-number variation, with pronounced lineage-specific expansions. Ka/Ks analyses indicated pervasive purifying selection (median 0.516) but heterogeneous constraints among subfamilies. Finally, cultivated tea showed higher TPS expression in most tissues, especially mature leaf and stem, and TPS-g displayed the broadest and strongest expression. Together, these results provide a pan-genome resource for Camellia TPSs and highlight how domestication, duplication, and CNV shape terpene-related genetic diversity. Full article

Individuals born after intrauterine growth restriction (IUGR) are at increased risk of long-term cardiovascular complications, including elevated blood pressure, endothelial dysfunction, and arterial stiffness. Endothelial progenitor cells (EPCs), particularly endothelial colony-forming cells (ECFCs), play a critical role in maintaining vascular homeostasis. Previously, Simoncini et al. observed that in a rat model of IUGR, six-month-old males exhibited elevated systolic blood pressure (SBP) and microvascular rarefaction compared with control (CTRL) rats. These vascular alterations were accompanied by reduced numbers and impaired function of bone marrow-derived ECFCs, which were associated with oxidative stress and stress-induced premature senescence (SIPS). In contrast, IUGR females of the same age and from the same litter did not exhibit higher SBP or microvascular rarefaction, raising the question of whether ECFC dysfunction in IUGR female rats can be present without vascular alterations. So, we investigated ECFCs isolated from six-month-old female IUGR offspring (maternal 9% casein diet) and CTRL females (23% casein diet). To complete the vascular assessment, we performed in vivo and in vitro investigations. No alteration in pulse wave velocity (measured by echo-Doppler) was observed; however, IUGR females showed decreased aortic collagen and increased elastin content compared with CTRL. Regarding ECFCs, those from IUGR females maintained their endothelial identity (CD31⁺/CD146⁺ ratio among viable CD45⁻ cells) but exhibited slight alterations in progenitor marker expression (CD34) compared with those of CTRL females. Functionally, IUGR-ECFCs displayed a delayed proliferation phase between 6 and 24 h, while their ability to form capillary-like structures remained unchanged, however their capacity to form capillary-like structures was preserved. Regarding the nitric oxide (NO) pathway, a biologically relevant trend toward reduced NO levels and decreased endothelial nitric oxide synthase expression was observed, whereas oxidative stress and SIPS markers remained unchanged. Overall, these findings indicate that ECFCs from six-month-old female IUGR rats exhibit only minor functional alterations, which may contribute to vascular protection against increase SBP, microvascular rarefaction, and arterial stiffness. Full article

Developing sustainable and molecularly selective adsorbents for heavy-metal removal remains a critical challenge in water purification. Herein, we report a green molecular-engineering approach for fabricating aza-crown ether functionalized sodium alginate aerogels (ACSA) capable of highly selective Cu²⁺ capture. The aerogels were synthesized via saccharide-ring oxidation, Cu²⁺-templated self-assembly, and reductive amination, enabling the covalent integration of aza-crown ether motifs within a hierarchically porous biopolymer matrix. Structural analyses (FTIR, ¹³C NMR, XPS, SEM, TGA) confirmed the in situ formation of macrocyclic N/O coordination sites. Owing to their interconnected porosity and chemically stable framework, ACSA exhibited rapid sorption kinetics following a pseudo-second-order model (R² = 0.999) and a Langmuir maximum adsorption capacity of 150.82 mg·g⁻¹. The material displayed remarkable Cu²⁺ selectivity over Zn²⁺, Cd²⁺, and Ni²⁺, arising from the precise alignment between Cu²⁺ ionic radius (0.73 Å) and crown-cavity dimensions, synergistic N/O chelation, and Jahn-Teller stabilization. Over four regeneration cycles, ACSA retained more than 80% of its original adsorption capacity, confirming excellent durability and reusability. This saccharide-ring modification strategy eliminates crown-ether leaching and weak anchoring, offering a scalable and environmentally benign route to bio-based adsorbents that combine molecular recognition with structural stability for efficient Cu²⁺ remediation and beyond. Full article

Geometric discontinuities are unavoidable in additively manufactured polymer components and can significantly alter their mechanical response; however, their effects are rarely quantified in a systematic and geometry-comparative manner. In this study, the tensile behavior of FDM-printed PLA+ specimens with three different geometries—dog-bone, circular-hole, and U-notched (manufactured and tested in accordance with ASTM D638 (Type IV))—was experimentally and numerically investigated. Tensile tests were conducted using a universal testing machine equipped with an extensometer, while finite element simulations were performed using an experimentally calibrated Ramberg–Osgood-based elastic–plastic material model. The dog-bone specimens exhibited an ultimate tensile strength (UTS) of 41–43 MPa and a Young’s modulus of 3.06 GPa, representing the intrinsic material response under nearly homogeneous stress conditions. Circular-hole specimens maintained comparable strength (38–42 MPa) but showed reduced ductility (1.4–1.6%) and a slightly increased apparent modulus of 3.17 GPa due to localized deformation. In contrast, U-notched specimens displayed the highest apparent modulus (≈5.30 GPa) and nominal UTS (46–49 MPa), accompanied by a pronounced reduction in ductility (0.9–1.0%), indicating severe stress concentration and predominantly brittle fracture behavior. Finite element analysis showed excellent agreement with experimental results, with peak von Mises stresses reaching approximately 42 MPa for all geometries, corresponding closely to the experimentally measured tensile strength. These results demonstrate that geometric discontinuities strongly govern stress localization, apparent stiffness, and fracture initiation in FDM-printed PLA+ components. The validated Ramberg–Osgood-based modeling framework provides a reliable tool for predicting geometry-dependent mechanical behavior under quasi-static loading and supports geometry-aware design of additively manufactured polymer structures. Full article

Engineered skin (ES) can serve as an advanced therapy for treatment of large full-thickness wounds, but delayed vascularization can cause ischemia, necrosis, and graft failure. To accelerate ES vascularization, this study assessed incorporation of polydopamine (PDA) microparticles loaded with different concentrations of basic fibroblast growth factor (bFGF) into collagen scaffolds, which were subsequently seeded with human fibroblasts to create dermal templates (DTs), and then keratinocytes to create ES. DTs and ES were evaluated in vitro and following grafting to full-thickness wounds in immunodeficient mice. In vitro, metabolic activity of DTs was enhanced with PDA+bFGF, though this increase was not observed following seeding with keratinocytes to generate ES. After grafting, ES with bFGF-loaded PDA microparticles displayed dose-dependent increases in CD31-positive vessel formation vs. PDA-only controls (p < 0.001 at day 7; p < 0.05 at day 14). Interestingly, ES containing PDA+bFGF microparticles exhibited an almost 3-fold increase in water loss through the skin and a less-organized basal keratinocyte layer at day 14 post-grafting vs. controls. This was associated with significantly increased inflammatory cell infiltrate vs. controls at day 7 in vivo (p < 0.001). The results demonstrate that PDA microparticles are a viable method for delivery of growth factors in ES. However, further investigation of bFGF concentrations, and/or investigation of alternative growth factors, will be required to promote vascularization while reducing inflammation and maintaining epidermal health. Full article

Piscine lactococcosis is an emerging bacterial disease that threatens freshwater and marine aquaculture in the Mediterranean region. This study characterized isolates of Lactococcus garvieae and Lactococcus petauri from farmed fish through molecular identification, genomic typing and antimicrobial susceptibility testing. A total of 39 bacterial strains were analyzed using species-specific real-time PCR assays, multilocus sequence typing and broth microdilution to determine minimum inhibitory concentrations. Results suggest a temporal shift in freshwater systems, where L. garvieae predominated in earlier isolates (mainly ST13, CC4), while L. petauri (ST14, CC14) appears as the dominant species in recent years. In marine fish, only L. garvieae was detected, mainly ST95 (CC95), a lineage previously reported in Europe. Molecular variability was found in both species with lineages capable of infecting livestock and humans. Amoxicillin displayed promising results; florfenicol showed moderate activity, while flumequine exhibited no inhibitory effect. Oxytetracycline and trimethoprim–sulfamethoxazole showed variable results requiring prudent use. These region-specific susceptibility profiles provide updated baseline data to guide empirical antimicrobial therapy while awaiting laboratory confirmation, highlighting the evolution of lactococcosis in aquaculture and emphasizing the need for molecular surveillance, antimicrobial stewardship, and vaccine updates within a One Health framework to mitigate impacts on Mediterranean aquaculture and public health. Full article

Developing a deep understanding of the evolutionary driving mechanisms of university–industry collaborative innovation networks among Chinese cities is of great significance for advancing sustainable urban development. Based on university–industry collaborative patent data from 275 prefecture-level and above cities in China during the period 2004–2020, this study constructs an intercity university–industry collaborative innovation network and employs the temporal exponential random graph model to analyze its evolutionary driving mechanisms. The results indicate that the network structure has become increasingly complex over time and exhibits pronounced small-world characteristics in the later stages. Network formation is distinctly non-random and is jointly shaped by endogenous structural effects and exogenous factors. Diffusion, connectivity, and closure effects are all significant, while intercity collaborative ties are influenced by multidimensional proximity, including economic, geographic, and organizational proximity. Moreover, the network structure demonstrates strong temporal stability. In the context of high-intensity collaboration, cities place greater emphasis on economic and organizational proximity, and cities with higher levels of economic development and prior experience in high-intensity collaboration are more likely to establish collaborative ties. Furthermore, eastern cities tend to collaborate with partners at similar levels of economic development, whereas cities in central and western regions display a more pronounced core–periphery pattern. Overall, from the perspective of intercity university–industry collaborative innovation networks, this study provides new empirical evidence and insights for promoting coordinated regional innovation capacity and sustainable urban development. Full article

This study investigates the reuse of mechanically recycled polyester–glass thermoset scraps (PS) as fillers in LDPE and HDPE matrices at 10–50 wt.% loading. Composites were produced through mechanical size reduction, single-screw extrusion, and compression molding without compatibilizers, and their mechanical and microstructural properties were systematically evaluated. LDPE composites exhibited a notable stiffness increase, with tensile modulus rising from 318.8 MPa (neat) to 1245.6 MPA (+291%) and tensile strength improving from 9.50 to 11.45 MPa (+20.5%). Flexural performance showed even stronger reinforcement: flexural modulus increased from 0.40 to 3.00 GPa (+650%) and flexural strength from 14.5 to 35.6 MPa (+145%). HDPE composites displayed similar behavior, with flexural modulus increasing from 1.2 to 3.1 GPa (+158%) and strength from 34.1 to 45.5 MPa (+33%). Surface-treated fillers provided additional stiffness gains (+36% in sPL4; +33% in sPH3). Impact strength decreased with loading (LDPE: −51%, HDPE: −61%), though surface treatment partially mitigated this (+14–19% in LDPE; +13% in HDPE). Density increased proportionally (PL: 0.95 → 1.20 g/cm³, PH: 0.99 → 1.23 g/cm³), while moisture uptake remained low (≤0.25%). Optical and SEM analyses indicated increasingly interconnected fiber networks at high loadings, driving stiffness and fracture behavior. Overall, PS-filled polyolefins offer a scalable route for converting thermoset waste into functional semi-structural materials. Full article

Recently, the EU approved RENURE-criteria materials to be used as substitutes for synthetic N fertilisers. Several studies have been performed on the agronomic efficacy and potential environmental impacts of different bio-based fertilisers (BBFs) from biomass recovery, including the RENURE-criteria materials. But information is lacking about their effectiveness under abiotic stress conditions like salinity and drought. The predictions for climate change-induced increased drought and soil salinisation for the European soils have also increased, making it inevitable to understand BBF performance in these impending situations. Two RENURE-criteria top-priority materials (ammonium nitrate (AN) and ammonium sulphate (AS) and another commercially used BBF—an evaporator concentrate (CaE)) were evaluated in a pot trial growing spinach under salinity and drought stress with a reference ‘no stress’ condition to examine crop growth, nutrient uptake, and nitrogen fertiliser replacement value (NFRV). Agronomically, BBFs performed at par with the synthetic fertiliser (SF) under unstressed and salt-stressed conditions, whereas, under drought stress, BBFs outperformed the SF treatment. AS exhibited the highest yield and nutrient uptake, displaying an NFRV of 3.1 and 1.8 under no-stress and salt-stress conditions, respectively. Salt stress did not negatively impact the crops grown in this trial, potentially due to the higher potassium content in the system, which alleviated the possible negative impacts of high sodium. This study delves into the agronomic response, without evaluating crop physiological changes, and, hence, should be taken as a preliminary step into further investigation of observed elemental interactions (that could be potentially driving stress mitigation) while also examining the crop physiology during the duration of stress. Full article

Background/Objectives: Cancer persists as a leading concern in the current medical field, and current therapies are limited by toxicity, cost, and resistance. Targeted inhibition of tubulin polymerization is considered as a promising therapeutic strategy for cancer treatment. Methods: Thirty-one new tubulin polymerization inhibitors were designed via molecular hybridization techniques, and BLI technology was employed to quantitatively investigate their interactions with tubulin. Antiproliferative activities against MCF-7, MDA-MB-231, A549, and HeLa cell lines was evaluated using the CCK8 assay. Apoptosis induction and cell cycle arrest were analyzed by flow cytometry. The anti-tumor activity of compound B6 was validated in a mouse melanoma tumor model. Results: Compounds exhibited varying degrees of antiproliferative activity against four tumor cell lines. Among them, compound B6 was the most promising candidate and displayed strong broad-spectrum anticancer activity with an average IC₅₀ value of 2 μM. The mechanism studies revealed that compound B6 inhibited tubulin polymerization in vitro, disrupted cell microtubule networks, and arrested the cell cycle at G2/M phase. Furthermore, B6 displayed significant in vivo antitumor efficacy in a melanoma tumor model with tumor growth inhibition rates of 70.21% (50 mg/kg). Conclusions: This work shows that B6 is a promising lead compound deserving further investigation as a potential anticancer agent. Full article