Search Results (16,936)

Chondrosarcoma (CHS), the second most common primary malignant cartilage tumor, is largely resistant to conventional therapies, making surgical resection the standard treatment. Proton therapy offers a physical advantage through the Bragg peak, enabling targeted irradiation while sparing surrounding tissues. However, differential biological responses between malignant and normal cartilage cells remain poorly understood. In this study, CHS SW1353 cells and normal chondrocytes (MC615) were exposed to proton irradiation. Biological responses were assessed via clonogenic survival, cell viability, apoptosis (caspase 3/7), micronucleus formation, cell cycle profiling, and oxidative stress markers. Proteomic changes were analyzed using mass spectrometry and bioinformatics. CHS cells exhibited higher radioresistance (D₁₀ = 6.45 Gy) than normal chondrocytes (D₁₀ = 5.08 Gy), oxidative stress adaptation, G1 arrest and proteomic plasticity, whereas normal chondrocytes displayed increased oxidative stress, extracellular matrix fragility and impaired integrin signaling. Notably, the tumor-specific increased levels of Tyrosine-protein kinase Fyn and Yes1-associated transcriptional regulator (YAP1) signaling suggest molecular drivers of radioresistance. Overall, proton irradiation elicits distinct biological and proteomic responses in malignant versus normal cartilage cells. These findings highlight potential radiosensitization targets, including Fyn/Src and YAP1/Hippo pathways, while underscoring the need to optimize proton therapy to enhance tumor control while minimizing damage to healthy cartilage. Full article

Ceratitis capitata (Diptera: Tephritidae), or medfly, is an invasive pest widespread in Argentina, where standardized management methods, such as cultural and chemical controls, are commonly implemented. The success in controlling medfly populations depends on implementing preventive, sustainable, long-term, and eco-friendly eradication/control strategies across all invaded environments. One strategy may involve augmentative biological control using parasitoids adapted to local conditions, such as Ganaspis pelleranoi (Brèthes) (Hymenoptera: Figitidae), a Neotropical-native parasitoid that mostly forages on tephritid larvae in a broad range of fallen fruit. Two hypotheses were tested in the current study: (1) G. pelleranoi females are more efficient in controlling medfly larvae infesting different fruits as the density of released females progressively increases, and (2) such parasitoid-induced host mortality capacity remains when host density is increased. Parasitism (reproductive effects) and additional host mortality (non-reproductive effects) were the indicator variables of parasitoid-induced host ability. Trials were performed in field cages (semi-field conditions) using two medfly-multiplier host fruit species, namely sour orange and peach, and with variations in both parasitoid release and host larval densities. Three major findings were highlighted: (1) G. pelleranoi females successfully parasitized host larvae on peach and sour orange, regardless of their strongly differing physical features, although medfly larvae in peaches were significantly more susceptible to the parasitoid; (2) medfly mortality significantly increased in both peach and sour orange relative to the gradual increase in released G. pelleranoi females, regardless of the increase in host density offered to parasitoids; and (3) G. pelleranoi females induced a substantially high host die-off rate when the additional mortality was added to the analysis, which was not revealed when parasitism alone was regarded as a medfly mortality variable. Such outcomes may provide relevant information for implementing an augmentative biological control against medfly using indigenous parasitoid species within an eco-friendly fruit fly pest management approach. Full article

In this study, we aimed to examine the multiplicative interaction model as a tool to assess the impact of plant extracts and fermentation products on the growth of mycelium of selected fungi. The materials used in the study included a total of 16 products. Plant extracts were obtained by the processes of ultrasound-assisted extraction (UAE) or supercritical CO₂ extraction, and the fermentation broths were produced by Enterobacter and Paenibacillus bacteria in a bioreactor. All these products were examined in vitro using 12 cultures of frequently occuring pathogenic fungi collected from cereals and oilseed rape cultivation. For mycelium diameter in all three examined concentrations, the Additive Main impacts and Multiplicative Interaction (AMMI) analyses showed substantial impacts of both the product and the pathogen as well as the product-by-pathogen interaction. It is advised that future plant protection techniques incorporate product E8, a plant extract (the CO₂ extract of a ginger plant belonging to the Zingiberaceae family), since it demonstrated excellent stability and good average mycelium diameter values across all concentrations examined. As far as the authors are aware, this is the first time the AMMI model has been used to evaluate the impact of product–pathogen interactions on mycelium diameter. Full article

In June 2023, a larva of grassland caterpillar Gynaephora qinghaiensis naturally infected by an entomopathogenic fungus was collected from an alpine rangeland in Gangcha County, Haibei Tibetan Autonomous Prefecture, Qinghai Province. After laboratory isolation and cultivation, the pathogen was identified as Beauveria bassiana (designated as GC23620) based on morphological characteristics and ITS-rDNA sequence similarity analysis. The larvicidal efficacy of B. bassiana GC23620 against fourth-instar larvae of G. qinghaiensis were assessed using two inoculation methods in laboratory conditions. The infection process and pathogenicity were analyzed by simulation and parameter estimation using the Time–Dose–Mortality (TDM) model. The estimated parameters for the concentration effect of strain GC23620 (β) were 0.56 (leaf dipping method) and 0.30 (insect immersion method), respectively. After treatment with conidial suspensions (1.05 × 10⁵ to 1.05 × 10⁹ conidia/mL), the cumulative corrected mortalities were 72.73–100.00% (leaf dipping method) and 42.42–90.91% (insect immersion method) at 8 days after inoculation (DAI), and the median lethal doses (LD₅₀) decreased to 1.74 × 10³ conidia/mL (leaf dipping method) and 1.85 × 10⁴ conidia/mL (insect immersion method), respectively, during the same post-inoculation period. After inoculation with conidial suspension under a concentration of 1.05 × 10⁶ conidia/mL, the median lethal times (LT₅₀) were 2.40 (leaf dipping method) and 4.51 days (insect immersion method). A control efficacy of 84.27% was obtained for G. qinghaiensis larvae on grassland at 21 days post-treatment after spraying the fermentation solution with a low dose of 1.05 × 10⁵ conidia/mL. In conclusion, B. bassiana strain GC23620 exhibited high pathogenic activity against G. qinghaiensis larvae and has strong potential for the green control of grassland pests. Full article

As natural nanoscale intercellular messengers, exosomes exhibit considerable potential in modulating inflammation, angiogenesis, immunoregulation, and tissue remodeling, making them attractive candidates for regenerative medicine. However, their clinical translation remains limited by rapid systemic clearance, nonspecific biodistribution, insufficient lesion retention, and functional attenuation in hostile pathological microenvironments. In this review, we propose that biomaterial engineering should evolve from providing passive exosome carriers to constructing active regulatory platforms capable of precise spatiotemporal control. We summarize engineering strategies along two complementary dimensions. In the temporal dimension, biomaterials can enable sustained, sequential, or microenvironment-responsive release to match the dynamic phases of tissue repair. In the spatial dimension, biomaterials can improve local retention, tissue anchoring, structural guidance, endogenous cell recruitment, and lesion-specific delivery. Using cutaneous wound healing, osteochondral regeneration, myocardial repair, and neural regeneration as representative examples, we further analyze these strategies through a “clinical challenge–engineering strategy–biological mechanism” framework, with particular attention to how engineered systems influence key signaling pathways such as PI3K/Akt, Wnt/β-catenin, NF-κB, and PTEN/PI3K/Akt/mTOR. We also discuss translational barriers, including exosome heterogeneity, safety concerns inherited from parental cells, large-scale GMP-compliant manufacturing, product standardization, storage stability, and regulatory classification of exosome–biomaterial hybrids. Finally, we highlight emerging directions, including multi-mechanism combinational systems, closed-loop responsive platforms, and artificial intelligence-assisted design for personalized exosome therapeutics. This review provides a design-oriented framework to accelerate the bench-to-bedside development of biomaterial-enabled precision exosome therapy. Full article

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by progressive bone marrow fibrosis, extramedullary hematopoiesis (particularly symptomatic splenomegaly), constitutional symptoms, progressive cytopenias, and, in a subset of patients, leukemic transformation. The advent of the JAK1/2 inhibitor ruxolitinib has revolutionized the management of MF, substantially improving splenomegaly, symptom burden, and, in some settings, overall survival. However, a substantial percentage of patients fail to achieve sustained benefit, are intolerant, or become refractory; real-world and clinical trial data indicate that approximately half of treated patients discontinue ruxolitinib treatment within 3 years and up to approximately 75% within 5 years, with poor outcomes after discontinuation (median survival in several series is approximately 12–14 months). In recent years, several new small molecules that act beyond the JAK-STAT axis have emerged in clinical development. These include agents targeting telomerase (imetelstat), epigenetic regulation via BET inhibition (pelabresib/CPI-0610), the MDM2-p53 axis (navtemadlin/KRT-232), erythroid maturation and the bone marrow microenvironment (luspatercept), PI3K signaling (parsaclisib), and PIM inhibitors (nuvisertib). Early clinical data show promising results for symptom and splenic control in specific settings and, importantly, suggest potential disease-modifying activity (improvements in marrow fibrosis and molecular responses) for some compounds. This review summarizes the biological rationale, key clinical data (efficacy and safety), ongoing randomized trials, and remaining knowledge gaps for these non-JAK small molecules in MF and offers practical considerations for integrating them into contemporary treatment algorithms. Full article

This study has investigated the occurrence characteristics and population damage of weeds in double-cropping direct-seeded rice fields in Hunan, and has identified efficient and safe pre- and post-emergence herbicides to enhance resistance management. Field trials were conducted at two representative sites (Yiyang and Changsha) in Hunan in 2024~2025. Weed community composition and emergence patterns were systematically monitored. The inhibitory effects of weed infestations on rice growth and yield were quantified. The biological activity and field efficacy of various herbicide classes against barnyardgrass (Echinochloa crus-galli) were evaluated via greenhouse bioassays and field trials. Weed emergence lasted 3–48 days after sowing (DAS) with three distinct peaks. Grasses emerged earliest and dominated the community, with barnyardgrass peaking at 13–17 DAS (≈50% of total weeds), followed by broadleaves at 20 DAS (≈40%) and sedges at 25 DAS (<20%). Weed infestation drastically suppressed rice height (max 19% reduction) and tillering (max 50% reduction), with mixed-weed and grass-dominated plots causing the severest yield losses (92.0% and 90.5%, respectively), versus only 18.0% in broadleaf-dominated plots. Greenhouse bioassays showed that oxaziclomefone had the highest intrinsic activity against barnyardgrass (GR₉₀ = 17.70 g ai ha⁻¹). In pre-emergence applications in field trials, pretilachlor (900 g ai ha⁻¹) and mefenacet (147.6 g ai ha⁻¹) provided >96.8% control at 20 and 40 days after treatment (DAT), while oxaziclomefone (66 g ai ha⁻¹) achieved 88.2% control at 20 DAT. For post-emergence herbicides, Profoxydim showed the highest intrinsic activity (GR₉₀ = 33.01 g ai ha⁻¹), followed by feproxydim (GR₉₀ = 33.45 g ai ha⁻¹) and flusulfinam (GR₉₀ = 64.55 g ai ha⁻¹). In field trials, flusulfinam provided 100% control with superior crop safety at 20 and 40 DAT, while Florpyrauxifen-benzyl, feproxydim, and metamifop reached >93% efficacy. In conclusion, weed emergence in Hunan direct-seeded rice follows a three-peak pattern, with barnyardgrass being the most destructive species. An integrated strategy combining pretilachlor (pre-emergence) and flusulfinam (post-emergence), rotated with florpyrauxifen-benzyl and feproxydim, is recommended for effective barnyardgrass management and resistance mitigation. Full article

Some actinobacterial species have been reported to improve plant growth due to their roles as biostimulants and biological control agents. In this study, the effect of actinobacterial isolate 27, obtained from the rhizospheric soil of melon plants and identified as Streptomyces calvus, was evaluated on the growth of Arabidopsis thaliana and tomato plants. In Arabidopsis, in vitro assays showed that after seven days of interaction, isolate 27 increased fresh weight by 1.4-, 1.5-, and 2.3-fold and lateral root number by 1.7-, 1.3-, and 2.5-fold under physical contact and split-plate systems (MS and ISP2 media), respectively, compared with non-inoculated plants. An increased β-glucuronidase (GUS, encoded by the uidA gene) signal was observed in primary and lateral roots of the Arabidopsis DR5::uidA reporter line during both interaction types, suggesting the activation of auxin-responsive pathways. In addition, isolate 27 rescued the rhd6 (root hair defective 6) mutant phenotype, restoring root hair formation. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that isolate 27 emitted volatile organic compounds (VOCs), including an alcohol and several sesquiterpenes, and that this profile changed during interaction with Arabidopsis plantlets. In soil-based pot assays, inoculation with isolate 27 significantly enhanced the development of Arabidopsis plants after 23 days, both when applied alone and in co-inoculation with Trichoderma atroviride. Furthermore, isolate 27 stimulated tomato plant growth, leading to significant increases in fresh and dry biomass, as well as shoot and root lengths after 28 days. Overall, these results demonstrate that S. calvus isolate 27 promotes plant growth and development through the production of bioactive compounds that modulate plant growth pathways, including hormonal responses, highlighting its potential as a bioinoculant for sustainable and productive agricultural systems. Full article

Microbial communities associated with the rhizosphere and phyllosphere are recognized as fundamental components influencing essential plant processes, including nutrient acquisition, growth promotion, and tolerance to stress. Biological control agents (BCAs), such as Trichoderma spp. and Bacillus spp., are widely applied in citrus crops. However, while BCAs effectiveness against plant pathogens is widely established, their resulting impact on indigenous, non-target bacterial and fungal communities remains poorly understood. The aim of this study was to evaluate the non-target effects of two commercial microbial formulations—one containing Trichoderma asperellum ICC 012 and T. gamsii ICC 080, and the other Bacillus amyloliquefaciens QST 713—on the resident microbiomes of Citrus volkameriana seedlings by using the amplicon-based metagenomic analysis, targeting the 16S rRNA and ITS1 regions. The application of the Trichoderma formulation as a soil drench in the rhizosphere resulted in minimal changes to the overall composition and diversity (α- and β-diversity) of the bacterial communities. This stability is considered a desirable trait for overall soil health. However, specific taxonomic changes were observed, such as a notable decrease in the genus Rhodococcus (0.4% vs. 1.5% in controls) among bacteria. In the fungal communities, the treatment led to a significant shift in phylum relative abundance, characterized by an increase in Basidiomycota (38% vs. 28% in controls) and a corresponding decrease in Ascomycota (51% vs. 56% in controls). Successful colonization was confirmed by a substantially higher relative abundance of the inoculated Trichoderma genus compared to control plants (1.4% vs. 0.1% in controls). Conversely, the foliar application of the Bacillus product induced a substantial restructuring of the phyllosphere bacterial community. This treatment caused a statistically significant reduction in bacterial α-diversity and a clear differentiation in community composition (β-diversity) relative to untreated controls. The successful colonization by the BCA resulted in the dominance of the Bacillus genus in the treated samples (27% vs. 2% in controls). Importantly, this ecological shift was accompanied by the enrichment of other beneficial bacterial taxa, including Sphingomonas (15% vs. 4% in controls) and the Burkholderia-Caballeronia-Paraburkholderia group (4% vs. 2% in controls). While fungal phyla abundances remained generally stable in the phyllosphere, specific genera such as Cladosporium (15% vs. 23% in controls) and Symmetrospora (21% vs. 13% in controls) prevailed post-treatment. In conclusion, these findings highlight the importance of considering non-target microbiome shift when implementing microbial biocontrol strategies in citrus production systems, since in this study was demonstrated that commercial BCAs exert a markedly differential influence based on the compartment of application: Trichoderma promoted ecological stability in the rhizosphere, whereas Bacillus induced a directional community shift in the phyllosphere. Full article

We performed a protein-docking study for eight DNA aptamers (SEQ1–SEQ8) against chicken Cluster of Differentiation 40 (chCD40), which were experimentally identified via SELEX in our previous study. In silico and molecular docking analyses were performed to predict and obtain the secondary and tertiary structures of the aptamers. Aptamers SEQ3 and SEQ4, which showed the best inhibitory effects, were selected and utilized to produce a DNA-based vaccine adjuvant using rolling circle amplification (RCA). These aptamers had been previously characterized via mass spectroscopy to determine their molecular weight and regions that could potentially interact with chCD40. In the present study, these results were corroborated and expanded. A series of free software methods, including Mfold v.1.0, 3dADN v.2.0, ClusPro v.2.0, Hdock v.1.0, and PLIP v.1.0, were used to determine the aptamers’ secondary and tertiary structures and docking interactions, as well as the specific residues involved in the interactions and their distances. The structures were used to explain and thus understand their effect on the binding, selectivity, and stability of the aptamers. The main objective of the study was to determine whether these aptamers could be used as vaccine adjuvants against viral and bacterial pathogens, specifically chicken avian influenza. The docking results were in good agreement with the experimental and biological results. The procedure employed in this study could be an easy and effective tool for exploring the potential of the new technology of systematic evolution of ligands by exponential enrichment (SELEX) in the preparation of aptamers to control viral and bacterial infections as well as diseases, such as cancer and Alzheimer’s. Full article

This review comprehensively examines the incorporation of nanoparticles (NPs) into biopolymers for 3D printing in biomedical applications, integrating material design, processing strategies, and translational considerations within a unified framework. Different types of NPs are analyzed regarding their effects on mechanical reinforcement, rheological modulation, and structural organization of biopolymeric matrices. The discussion covers principal additive manufacturing technologies, including extrusion-based systems such as fused deposition modeling (FDM) and direct ink writing (DIW), vat photopolymerization, powder-bed fusion (SLS), and emerging in situ nanoparticle formation approaches, emphasizing how nanoparticle loading and surface functionalization govern yield stress, shear-thinning behavior, viscoelastic recovery, and dimensional fidelity while mitigating agglomeration and optimizing interfacial interactions. Comparative evaluation of compressive modulus, strength, toughness, crystallinity, and porosity establishes structure–property–processing relationships directly linked to printability and functional performance. Biomedical applications are addressed in tissue engineering, biosensing, controlled and targeted drug delivery, and bioimaging, highlighting the balance between bioactivity and manufacturability. Finally, critical challenges—including compatibility, reproducibility, biological safety, long-term stability, regulatory adaptation, and environmental impact—are discussed, alongside future perspectives focused on green nanomaterials, AI-driven predictive formulation design, and digital twins for real-time monitoring and quality control in nano-enabled additive manufacturing. Full article

Intestinal dysfunction and parenteral nutrition (PN) can trigger a spectrum of liver disorders collectively referred to as intestinal failure-associated liver disease (IFALD), for which therapeutic options remain limited. In the present study, we investigated the modulatory effects of the bioactive xanthophyll carotenoid lutein in an in vitro IFALD model utilizing human THLE-2 hepatocytes exposed to lipopolysaccharide and Intralipid to mimic PN–associated inflammatory and metabolic stress. Because lutein is poorly water-soluble and patients receiving PN lack enteral intake of this compound, we also evaluated the cyto- and hemocompatibility of a human serum albumin–based lutein nanoformulation developed to enable intravenous administration. A bead-based multiplex immunoassay revealed that lutein attenuated dysregulation of inflammatory and metabolic signaling by modulating total and phosphorylated levels of MAPKs, NF-κB, Akt, STAT5, CREB, and p70S6K. Lutein also affected lipid metabolism–related gene expression, decreasing SREBF2 and restoring ABCA1 and PRKAA2 mRNA toward control levels, as determined by qPCR. Nanoformulated lutein, with a mean particle size of approximately 160 nm, was non-toxic in THLE-2 cells and exhibited hemocompatibility in a human erythrocyte hemolysis assay. Together, our findings provide both biological and technological rationale for further exploration of lutein-based strategies to mitigate IFALD in patients receiving PN. Full article

Additive manufacturing enables the fabrication of patient-specific zirconia devices with integrated surface features; however, the biological effects of meso-scale topographies remain insufficiently understood. This in vitro study evaluated the influence of defined meso-scale surface modifications on osteoblast behavior using Digital Light Processing (DLP)-fabricated 3Y tetragonal zirconia polycrystal (3Y-TZP) and 5Y partially stabilized zirconia (5Y-PSZ). Planar control specimens and surfaces incorporating regularly distributed columnar structures (height: 100 µm; width: 40 µm; center-to-center spacing: 80, 120, and 160 µm; Mod-80, Mod-120, Mod-160) were fabricated and characterized after sintering. Cytotoxicity was assessed by elution testing and showed cell viability >98% for all groups. Osteoblast adhesion and proliferation (hFOB 1.19) were quantified using metabolic assays. Meso-scale modifications significantly increased early cell adhesion compared to planar controls (p < 0.05), with the strongest effect observed for Mod-160. No significant differences in proliferation rates were detected between groups (p > 0.05). Osteogenic differentiation was evaluated by RT-qPCR (RUNX2, ALPL, COL1A1, BGLAP), revealing material- and geometry-dependent responses. On 3Y-TZP, meso-scale structures, particularly Mod-160, were associated with sustained upregulation of BGLAP, whereas 5Y-PSZ exhibited less pronounced effects. Within the limitations of this in vitro study, meso-scale surface structuring of additively manufactured zirconia enhances early osteoblast adhesion without affecting proliferation and may influence osteogenic differentiation in a material-dependent manner. Full article

This study aimed to develop a novel fluorescent sensor based on Eu³⁺ complex-doped protein crystal (EC-PC) for the efficient detection of metal ions in blood. By meticulously controlling the crystallization and annealing conditions in the co-crystallization strategy, the crystal growth processes were optimized to obtain doped Eu³⁺ complex-co-protein crystalline (EC-PC) structures. Thus, through co-crystallization of hen egg white lysozyme (HEWL) as a model protein and Eu³⁺ complex as fluorescent center, we successfully prepared Eu³⁺ complex-doped-HEWL co-crystals (EC-HC) with excellent fluorescent properties. Further treatment with 4% glutaraldehyde cross-linking enhanced the structural stability of the co-crystals. Moreover, the characteristic of sensitive, selective quenching of EC-PC fluorescence by biologically relevant cations, such as Cu²⁺, Zn²⁺, Mg²⁺, Ca²⁺ and Fe³⁺ ions, set up a smart sensing system in blood. For example, the fluorescence intensity of the crystals at 610 nm, as measured by a UV–visible spectrophotometer, decreases dose-dependently with the concentration of copper ions, thereby validating the sensor’s high sensitivity to copper ion detection. Significantly, we also found that this hybrid protein-based sensor did not induce hemolysis, at various volume concentrations, confirming good anticoagulation in blood. This research not only provides a new perspective on the application of Eu³⁺ complex-doped protein crystals in the field of biosensing but also offers a new strategy for the detection of biologically relevant cations in blood. Future work will focus on further optimizing the sensor’s performance and exploring its potential applications in clinical sample analysis. Full article

The Soybean aphid (Aphis glycines) is a destructive pest that threatens soybeans. In order to develop green and effective control strategies, we propose an EQPAL epidemic model that integrates four developmental stages (1st–2nd stage nymphs, 3rd stage nymphs, 4th stage nymphs, and adults) and a ladybug (Harmonia axyridis) compartment. This model achieves green pest control by artificially releasing a natural enemy of soybean aphids to prey on adult soybean aphids. We analyzed the dynamic behavior of the model and derived the basic reproduction number ${\mathcal{R}}_0$. Using field monitoring data from Changchun City, Jilin Province, China in 2025, the segmented nonlinear least squares method was used for parameter estimation and fitting, resulting in an overall determination coefficient of $R^2=0.8204$. The numerical simulation results showed that the release of ladybugs significantly reduced the density and peak value of soybean aphid adults, and the predation rate $\beta$, predation conversion rate c, and ladybug migration rate $\omega$ were identified as key regulatory parameters. In addition, a cost–benefit analysis was conducted to determine the most cost-effective control measures. Full article