Search Results (1,459)

Cancer-associated fibroblasts (CAFs) restructure collagen hydrogels via actomyosin-driven fibril bundling and crosslinking, increasing polymer density to generate mechanical stress that accelerates tumor proliferation. Conventional hydrogel models lack spatial heterogeneity, thus obscuring how localized stiffness gradients regulate cell cycle progression. To address this, we developed a collagen hydrogel-based microtissue platform integrated with programmable microstrings (single/double tethering), enabling real-time quantification of gel densification mechanics and force transmission efficiency. Using this system combined with FUCCI cell cycle biosensors and molecular perturbations, we demonstrate that CAF-polarized contraction increases hydrogel stiffness (350 → 775 Pa) and reduces pore diameter (5.0 → 1.9 μm), activating YAP/TAZ nuclear translocation via collagen–integrin–actomyosin cascades. This drives a 2.4-fold proliferation increase and accelerates G1/S transition in breast cancer cells. Pharmacological inhibition of YAP (verteporfin), actomyosin (blebbistatin), or collagen disruption (collagenase) reversed mechanotransduction and proliferation. Partial rescue upon CYR61 knockdown revealed compensatory effector networks. Our work establishes CAF-remodeled hydrogels as biomechanical regulators of tumor growth and positions gel-based mechanotherapeutics as promising anti-cancer strategies. Full article

Pulmonary hypertension syndrome (PHS), a metabolic disorder causing economic losses in broilers, arises from hypoxia-induced portal hypertension and liver cirrhosis, triggering mitochondrial oxidative damage, excessive ROS production, and altered mitochondrial biogenesis. This study explored terpinen-4-ol (T4O), known for antimicrobial and anti-inflammatory properties, in mitigating PHS. Broilers were divided into four groups, including PHS-affected birds with/without T4O supplementation. Analyses revealed that PHS birds exhibited reduced antioxidant capacity, elevated MDA and ROS levels, increased mitochondrial numbers, and upregulated expression of oxidative stress markers (Keap1, HO-1, Nrf-2) and mitochondrial biogenesis regulators (PGC-1α, Nrf-1, Tfam). T4O administration enhanced antioxidant activity, reduced ROS and MDA, suppressed compensatory mitochondrial proliferation, and downregulated Keap1/Nrf-2 and mitochondrial biogenesis pathways. These effects suggest that T4O alleviates hypoxia-driven oxidative stress and mitochondrial dysfunction in broilers. Findings highlight T4O’s potential as a therapeutic agent to mitigate PHS-related losses in poultry production. Full article

RNA-binding proteins (RBPs), particularly IGF2BP3, play critical but underexplored roles in lung adenocarcinoma (LUAD). This study investigated IGF2BP3′s clinical and functional significance using single-cell/RNA sequencing, validated by qPCR, Western blot, and immunohistochemistry. The results show IGF2BP3 was significantly upregulated in LUAD tissues and associated with advanced-stage, larger tumors, lymph node metastasis, and poor prognosis. A prognostic nomogram confirmed its independent predictive value. Functionally, IGF2BP3 knockdown suppressed proliferation, and induced G2/M arrest and apoptosis. GSEA linked high IGF2BP3 to cell cycle activation and low expression to metabolic pathways. Notably, high IGF2BP3 correlated with immune evasion markers (downregulated CD4+ effector T cells, upregulated Th2 cells), while TIDE analysis suggested a better immunotherapy response in low-expressing patients. Drug screening identified BI-2536 as a potential therapy for low-IGF2BP3 cases, supported by strong molecular docking affinity (−7.55 kcal/mol). These findings establish IGF2BP3 as a key driver of LUAD progression and a promising target for immunotherapy and precision medicine. Full article

We report the development of highly luminescent, bovine serum albumin (BSA)-stabilized gold–silver bimetallic nanoclusters (Au-AgNCs@BSA) as a novel platform for high-sensitivity, ratiometric intracellular temperature sensing. Precise and non-invasive temperature sensing at the nanoscale is crucial for applications ranging from intracellular thermogenesis monitoring to localized hyperthermia therapies. Traditional luminescent thermometric platforms often suffer from limitations such as high cytotoxicity and low photostability. Here, we synthesized Au-AgNCs@BSA via a one-pot aqueous reaction, achieving significantly enhanced photoluminescence quantum yields (PL QYs, up to 18%) and superior thermal responsiveness compared to monometallic counterparts. The dual-emissive Au-AgNCs@BSA exhibit a linear ratiometric fluorescence response to temperature fluctuations within the physiological range (20–50 °C), enabling accurate and concentration-independent thermometry in live cells. Time-resolved PL and Arrhenius analyses reveal two distinct emissive states and a high thermal activation energy (E_a = 199 meV), indicating strong temperature dependence. Silver doping increases radiative decay rates while maintaining low non-radiative losses, thus amplifying fluorescence intensity and thermal sensitivity. Owing to their small size, excellent photostability, and low cytotoxicity, these nanoclusters were applied to non-invasive intracellular temperature mapping, presenting a promising luminescent nanothermometer for real-time cellular thermogenesis monitoring and advanced bioimaging applications. Full article

Three-dimensional printed polycaprolactone (PCL) tissue engineering scaffolds have drawn increasing interest from the medical industry due to their excellent biocompatibility and biodegradability, yet PCL’s poor mechanical performance has limited their applications. This study introduces a biocompatible and biodegradable polylactic acid (PLA) fiber reinforced PCL (PLA/PCL) composite as the filament for 3D printed scaffolds to significantly enhance their mechanical performance: Special-made PLA short fiber mat was infused with PCL matrix and rolled into PLA/PCL filaments through a “Vacuum Assisted Resin Infusion” (VARI) process. The investigation revealed that the PLA fibers are highly oriented along the printing direction when using this filament for 3D printing due to the unique microstructure formed during the VARI process. At the same PLA fiber content, the percentage increase in Young’s modulus of the 3D printed strands using the filaments produced by the VARI process is 127.6% higher than the 3D printed strands using the filaments produced by the conventional melt blending process. The 3D printed tissue engineering scaffolds using the PLA/PCL composite filament with 11 wt% PLA fiber content also achieved an exceptional 84.2% and 143.3% increase in peak load and stiffness compared to the neat PCL counterpart. Full article

With the accelerating global transition toward sustainable energy systems, power grids with a high share of renewable energy face increasing challenges due to volatility and uncertainty, necessitating advanced flexibility resource planning and stability optimization strategies. This paper presents a comprehensive distribution network planning framework that coordinates and integrates multiple types of flexibility resources through joint optimization and network reconfiguration to enhance system adaptability and operational resilience. A novel virtual network coupling modeling approach is proposed to address topological constraints during network reconfiguration, ensuring radial operation while allowing rapid topology adjustments to isolate faults and restore power supply. Furthermore, to mitigate the uncertainty and fault risks associated with extreme weather events, a CVaR-based risk quantification framework is incorporated into a bi-level optimization model, effectively balancing investment costs and operational risks under uncertainty. In this model, the upper-level planning stage optimizes the siting and sizing of flexibility resources, while the lower-level operational stage coordinates real-time dispatch strategies through demand response, energy storage operation, and dynamic network reconfiguration. Finally, a hybrid SA-PSO algorithm combined with conic programming is employed to enhance computational efficiency while ensuring high solution quality for practical system scales. Case study analyses demonstrate that, compared to single-resource configurations, the proposed coordinated planning of multiple flexibility resources can significantly reduce the total system cost and markedly improve system resilience under fault conditions. Full article

In order to improve the inversion accuracy of electrical resistivity tomography (ERT) and overcome the limitations of traditional linear methods, this paper proposes an improved shuffled frog leaping algorithm (SFLA). First, an equilibrium grouping strategy is designed to balance the contribution weight of each subgroup to the global optimal solution, suppressing the local optimum traps caused by the dominance of high-quality groups. Second, an adaptive movement operator is constructed to dynamically regulate the step size of the search, enhancing the guiding effect of the optimal solution. In synthetic data tests of three typical electrical models, including a high-resistivity anomaly with 5% random noise, a normal fault, and a reverse fault, the improved algorithm shows an approximately 2.3 times higher accuracy in boundary identification of the anomaly body compared to the least squares (LS) method and standard SFLA. Additionally, the root mean square error is reduced by 57%. In the engineering validation at the Baota Mountain mining area in Jurong, the improved SFLA inversion clearly reveals the undulating bedrock morphology. At a measuring point 55 m along the profile, the bedrock depth is 14.05 m (ZK3 verification value 12.0 m, error 17%), and at 96 m, the depth is 6.9 m (ZK2 verification value 6.7 m, error 3.0%). The characteristic of deeper bedrock to the south and shallower to the north is highly consistent with the terrain and drilling data (RMSE = 1.053). This algorithm provides reliable technical support for precise detection of complex geological structures using ERT. Full article

Magnetotelluric (MT) sounding is a crucial technique in mineral exploration. However, MT data are highly susceptible to various types of noise. Traditional data processing methods, which rely on the assumption of signal stationarity, often result in severe distortion when suppressing non-stationary noise. In this study, we propose a novel, adaptive, and less parameter-dependent signal decomposition method for MT signal denoising, based on time–frequency domain analysis and the application of modal decomposition. The method uses Variational Mode Decomposition (VMD) to adaptively decompose the MT signal into several intrinsic mode functions (IMFs), obtaining the instantaneous time–frequency energy distribution of the signal. Subsequently, robust statistical methods are introduced to extract the independent components of each IMF, thereby identifying signal and noise components within the decomposition results. Synthetic data experiments show that our method accurately separates high-amplitude non-stationary interference. Furthermore, it maintains stable decomposition results under various parameter settings, exhibiting strong robustness and low parameter dependency. When applied to field MT data, the method effectively filters out non-stationary noise, leading to significant improvements in both apparent resistivity and phase curves, indicating its practical value in mineral exploration. Full article

Objective: To investigate the effects of oat fiber on animal constipation and elucidate its underlying mechanisms. Methods: Male BALB/c mice were randomly allocated into five groups: control group (CON), model control group (MODEL), low dose group (LOW), middle dose group (MIDDLE), high dose group (HIGH). Constipation was induced in the mice by intragastric administration of loperamide. Subsequently, the mice (except those in the CON and MODEL groups) were administered oat fiber intragastrically for 21 consecutive days. Results: Compared with the MODEL group, oat fiber significantly increased the number of fecal pellets, fecal wet weight, and fecal water content (p < 0.05), shortened the time to first black stool excretion (p < 0.05), and enhanced the small intestinal propulsion rate in constipated mice. Additionally, oat fiber significantly upregulated motilin (MTL) and gastrin (GAS) levels (p < 0.05), while downregulating vasoactive intestinal peptide (VIP) and somatostatin (SS) levels (p < 0.05). It also significantly reduced the transcription level of Aquaporin 8 (AQP8) (p < 0.05), effectively alleviating intestinal mucosal injury and immune inflammation. The relative expression levels of TNF-α and IL-1β were significantly decreased in the oat fiber group (p < 0.05). Gut microbiota analysis revealed that oat fiber increased both the abundance and diversity of gut microbiota in constipated mice. Specifically, oat fiber was found to enhance the relative abundance of Firmicutes while reducing that of Bacteroidetes. At the genus level, it promoted the proliferation of Lachnospiraceae_NK4A136_group and Roseburia. Conclusions: Oat fiber alleviates constipation in mice by modulating gastrointestinal regulatory peptides, gut microbiota, aquaporin and mitigating intestinal barrier damage and immune-inflammatory responses. Full article

Construction wood has a high economic value, and its construction waste also has multiple consumption values. Natural wood has many advantages, such as thermal, environmental, and esthetic properties; however, wood sourced from artificial fast-growing forests is found to be deficient in mechanical strength. This shortcoming makes it less competitive in certain applications, leading many markets to remain dominated by non-renewable materials. To address this issue, various modification methods have been explored, with a focus on enhancing the plasticity and strength of wood. Studies have shown that hydrogen bonds in the internal structure of wood have a significant impact on its operational performance. Whether it is organic modification, inorganic modification, or a combination thereof, these methods will lead to a change in the shape of the hydrogen bond network between the components of the wood or will affect the process of its breaking and recombination, while increasing the formation of hydrogen bonds and related molecular synergistic effects and improving the overall operational performance of the wood. These modification methods not only increase productivity and meet the needs of efficient use and sustainable environmental protection but also elevate the wood industry to a higher level of technological advancement. This paper reviews the role of hydrogen bonding in wood modification, summarizes the mechanisms by which organic, inorganic, and composite modification methods regulate hydrogen bond networks, discusses their impacts on wood mechanical properties, dimensional stability, and environmental sustainability, and provides an important resource for future research and development. Full article

As the primary biological risk threatening safe dairy production, bovine mastitis control highly relies on environmental disinfection measures. However, the mechanisms by which chemical disinfectants influence host–environment microbial interactions remain unclear. This study systematically investigated the disinfection efficacy and regulatory effects on microbial community composition and diversity of glutaraldehyde-benzalkonium chloride (BAC) and glutaraldehyde-didecyl dimethyl ammonium bromide (DAB) at recommended concentrations (2–5%), using 80 environmental samples from intensive dairy farms in Xinjiang, China. Combining 16S rDNA sequencing with culturomics, the results showed that BAC achieved a disinfection rate of 99.33%, higher than DAB’s 97.87%, and reduced the environment–gut microbiota similarity index by 23.7% via a cationic bacteriostatic film effect. Microbiome analysis revealed that BAC selectively suppressed Fusobacteriota abundance (15.67% reduction) and promoted Bifidobacterium proliferation (7.42% increase), enhancing intestinal mucosal barrier function through butyrate metabolism. In contrast, DAB induced Actinobacteria enrichment in the environment (44.71%), inhibiting pathogen colonization via bioantagonism. BAC’s long-acting bacteriostatic properties significantly reduced disinfection costs and mastitis incidence. This study first elucidated the mechanism by which quaternary ammonium compound (QAC) disinfectants regulate host health through “environment-gut” microbial interactions, providing a critical theoretical basis for developing precision disinfection protocols integrating “cost reduction-efficiency enhancement-risk mitigation.” Full article

Cadmium (Cd) contamination in rice (Oryza sativa L.) poses serious health risks for human, necessitating effective mitigation strategies. This study investigated the effects of Cd stress on iron (Fe), manganese (Mn), zinc (Zn), and Cd accumulation and translocation in rice varieties with high (MY46) or low (ZS97B) Cd accumulation capacities grown in acidic and alkaline soils. Results demonstrated that Cd stress significantly inhibited plant growth, reducing plant height, shoot biomass, and grain yield in both soil types. Cd accumulation increased in roots, shoots, and grains, while Fe, Mn, and Zn concentrations decreased markedly. Molecular analysis revealed upregulation of metal transporter genes (OsIRT1, OsNRAMP1, OsNRAMP5) and the vacuolar sequestration gene (OsHMA3) in roots under Cd exposure. The translocation factor (TF) values of Mn and Zn from root to shoot were reduced in acidic soils, whereas Mn and Zn TFs exhibited an increasing trend in alkaline soils despite Cd exposure. Furthermore, correlation analyses indicated Mn and Zn play crucial roles in suppressing Cd accumulation in both acidic and alkaline soils. These findings provide critical insights for developing soil-specific strategies to reduce Cd accumulation in rice through micronutrient management. Full article

Burkholderia gladioli is a multifaceted bacterium with both pathogenic and beneficial strains, and nonpathogenic Burkholderia species have shown potential as plant growth-promoting rhizobacteria (PGPRs) and biocontrol agents. However, the molecular mechanisms underlying their beneficial functions remain poorly characterized. This study systematically investigated the antimicrobial mechanisms and plant growth-promoting properties of B. gladioli strain ZBSF BH07, isolated from the grape rhizosphere, by combining genomic and functional analyses, including whole-genome sequencing, gene annotation, phylogenetic and comparative genomics, in vitro antifungal assays, and plant growth promotion evaluations. The results showed that ZBSF BH07 exhibited broad-spectrum antifungal activity, inhibiting 14 grape pathogens with an average inhibition rate of 56.58% and showing dual preventive/curative effects against grape white rot, while also significantly promoting grape seedling growth with increases of 54.9% in plant height, 172.9% in root fresh weight, and 231.34% in root dry weight. Genomic analysis revealed an 8.56-Mb genome (two chromosomes and one plasmid) encoding 7431 genes and 26 secondary metabolite biosynthesis clusters (predominantly nonribosomal peptide synthetases), supporting its capacity for antifungal metabolite secretion, and functional analysis confirmed genes for indole-3-acetic acid (IAA) synthesis, phosphate solubilization, and siderophore production. These results demonstrate that ZBSF BH07 suppresses pathogens via antifungal metabolites and enhances grape growth through phytohormone regulation and nutrient acquisition, providing novel insights into the dual mechanisms of B. gladioli as a biocontrol and growth-promoting agent and laying a scientific foundation for developing sustainable grapevine disease management strategies. Full article

Background/Objectives: Digital food-related videos significantly influence cravings, appetite, and weight outcomes; however, the dynamic neural mechanisms underlying appetite fluctuations during naturalistic viewing remain unclear. This study aimed to identify neural activity patterns associated with moment-to-moment appetite changes during naturalistic food-cue video viewing and to examine their relationships with cravings and weight-related outcomes. Methods: Functional magnetic resonance imaging (fMRI) data were collected from 58 healthy female participants as they viewed naturalistic food-cue videos. Participants concurrently provided continuous ratings of their appetite levels throughout video viewing. Hidden Markov Modeling (HMM), combined with machine learning regression techniques, was employed to identify distinct neural states reflecting dynamic appetite fluctuations. Findings were independently validated using a shorter-duration food-cue video viewing task. Results: Distinct neural states characterized by heightened activation in default mode and frontoparietal networks consistently corresponded with increases in appetite ratings. Importantly, the higher expression of these appetite-related neural states correlated positively with participants’ Body Mass Index (BMI) and post-viewing food cravings. Furthermore, these neural states mediated the relationship between BMI and food craving levels. Longitudinal analyses revealed that the expression levels of appetite-related neural states predicted participants’ BMI trajectories over a subsequent six-month period. Participants experiencing BMI increases exhibited a significantly greater expression of these neural states compared to those whose BMI remained stable. Conclusions: Our findings elucidate how digital food cues dynamically modulate neural processes associated with appetite. These neural markers may serve as early indicators of obesity risk, offering valuable insights into the psychological and neurobiological mechanisms linking everyday media exposure to food cravings and weight management. Full article

Tuberous sclerosis complex (TSC) is a systemic disease caused by mutations in either the TSC1 (encoding hamartin) or TSC2 (encoding tuberin) gene, with mutations in the TSC2 gene potentially leading to more severe clinical symptoms. Neurological symptoms are a common clinical manifestation of TSC, and neuroinflammation is thought to play an important role. Glial cells are a major source of neuroinflammation, but whether microglia are involved in the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and the expression of interleukin-1β (IL-1β) in TSC patients remains unclear. We used a transcriptome sequencing dataset for bioinformatics analysis to explore the differences in the expression of microglial inflammasome-associated hub genes. TSC2 knockdown (TSC2 KD) microglia (HMC3 cell line) were generated by lentivirus, and the expression of inflammasome-associated hub genes, microglial activation, and NLRP3 inflammasome activation were verified. In addition, experiments were performed to explore the regulatory effects of rapamycin. Bioinformatics analysis identified a total of eight inflammasome-associated hub genes. By detecting GFP fluorescence, TSC2 mRNA, TSC2 protein expression, and the phosphorylation of the mammalian target of rapamycin (p-mTOR)/mTOR, we confirmed that the TSC2 KD microglia model was successfully established. Compared with the control group, the TSC2 KD group presented higher mRNA levels and fluorescence intensities of microglia AIF1 and CD68, as well as greater reactive oxygen species (ROS) production. Eight inflammasome-associated hub gene mRNA assays revealed that the expression of the NLRP3 and IL1B genes was increased. Compared with the control group, the TSC2 KD group presented increased levels of NLRP3 and Pro-IL-1β proteins in cells and Cleaved-Caspase 1 and Cleaved-IL-1β proteins in the supernatant, suggesting NLRP3 inflammasome activation. Rapamycin intervention alleviated these changes, demonstrating that the TSC2 gene regulation of microglial activation and NLRP3 inflammasome activation are correlated with mTOR phosphorylation. In conclusion, microglia are activated in TSC patients and participate in the NLRP3 inflammasome-associated neuroinflammatory response, and rapamycin treatment can alleviate these changes. Full article