Search Results (9,502)

Bone-related defects present a key challenge in orthopaedics. The current gold standard, autografts, poses significant limitations, such as donor site morbidity, limited supply, and poor morphological adaptability. This study investigates the potential of scaffold geometry to induce osteogenic differentiation of human adipose-derived stem cells (hADSCs) through mechanotransduction, without the use of chemical inducers. Four distinct poly-(L)-lactic acid (PLA) scaffold architectures—Traditional Cross (Tc), Triangle (T), Diamond (D), and Gyroid (G)—were fabricated using fused filament fabrication (FFF) 3D printing. hADSCs were cultured on these scaffolds, and their response was evaluated utilising an alkaline phosphatase (ALP) assay, immunofluorescence, and extensive proteomic analyses. The results showed the D scaffold to have the highest ALP activity, followed by Tc. Proteomics results showed that more than 1200 proteins were identified in each scaffold with unique proteins expressed in each scaffold, respectively Tc—204, T—194, D—244, and G—216. Bioinformatics analysis revealed structures with complex curvature to have an increased expression of proteins involved in mid- to late-stage osteogenesis signalling and differentiation pathways, while the Tc scaffold induced an increased expression of signalling and differentiation pathways pertaining to angiogenesis and early osteogenesis. Full article

Chronic kidney disease (CKD) remains a global health burden, with limited therapeutic options that effectively target the underlying pathophysiology. Nuclear factor erythroid 2-related factor 2 (NRF2), a key regulator of oxidative stress and inflammation, has garnered significant attention as a potential therapeutic target in CKD. Despite encouraging preclinical results, no NRF2-targeted agents have achieved clinical approval for CKD treatment. This review synthesizes emerging evidence showing substantial heterogeneity in NRF2 activity across CKD subtypes, influenced by disease etiology, CKD stage, and rate of disease progression. We elucidate the key therapeutic implications across diverse CKD etiologies and highlight that the therapeutic efficacy of NRF2 activation depends on precise modulation tailored to disease context. Although NRF2 overactivation and the need for stage-dependent modulation are increasingly recognized, this review further delineates the consequences of indiscriminate NRF2 activation, demonstrating that its effects diverge across CKD etiologies and cellular contexts. These insights support a nuanced, context-specific approach to NRF2-targeted strategies and provide a framework to guide future drug development in CKD. Full article

Water scarcity and spatial variability in soil fertility are key constraints to stable grain production in the Huang-Huai-Hai Plain. However, the interaction mechanisms between regulated deficit irrigation and soil fertility influencing yield formation and water-nitrogen use efficiency in winter wheat remain unclear. In this study, a two-year field experiment (2022–2024) was conducted to investigate the effects of two irrigation regimes—regulated deficit irrigation during the heading to grain filling stage (D) and full irrigation (W)—under four soil fertility levels: F1 (N: P: K = 201.84: 97.65: 199.05 kg ha⁻¹), F2 (278.52: 135: 275.4 kg ha⁻¹), F3 (348.15: 168.75: 344.25 kg ha⁻¹), and CK (no fertilization). The results show that aboveground dry matter accumulation, total nitrogen content, pre-anthesis dry matter and nitrogen translocation, and post-anthesis accumulation significantly increased with fertility level (p < 0.05). Regulated deficit irrigation promoted the contribution of post-anthesis dry matter to grain yield under the CK and F1 treatments, but suppressed it under the F2 and F3 treatments. However, it consistently enhanced the contribution of post-anthesis nitrogen to grain yield (p < 0.05) across all fertility levels. Higher fertility levels prolonged the grain filling duration by 18.04% but reduced the mean grain filling rate by 15.05%, whereas regulated deficit irrigation shortened the grain filling duration by 3.28% and increased the mean grain filling rate by 12.83% (p < 0.05). Grain yield significantly increased with improved fertility level (p < 0.05), reaching a maximum of 9361.98 kg·ha⁻¹ under the F3 treatment. Regulated deficit irrigation increased yield under the CK and F1 treatments but reduced it under the F2 and F3 treatments. Additionally, water use efficiency exhibited a parabolic response to fertility level and was significantly enhanced by regulated deficit irrigation. Nitrogen partial factor productivity (NPFP) declined with increasing fertility level (p < 0.05); Regulated deficit irrigation improved NPFP under the F1 treatment but reduced it under the F2 and F3 treatments. The highest NPFP (41.63 kg·kg⁻¹) was achieved under the DF1 treatment, which was 54.81% higher than that under the F3 treatment. TOPSIS analysis showed that regulated deficit irrigation combined with the F1 fertility level provided the optimal balance among yield, WUE, and NPFP. Therefore, implementing regulated deficit irrigation during the heading–grain filling stage under moderate fertility (F1) is recommended as the most effective strategy for achieving high yield and efficient resource utilization in winter wheat production in this region. Full article

In this study, we aimed to address the lack of systematic research on key collision dynamics parameters (elastic restitution coefficient) in the full mechanization of rapeseed operations, which hinders the development of precision agriculture. In this present work, the restitution coefficient of rapeseed was systematically investigated, and a predictive model (R² = 0.959) was also established by using Box–Behnken design response surface methodology (BBD-RSM). The results show that the collision restitution coefficient varies in the range of 0.539–0.649, with the key influencing factors ranked as follows: moisture content (M_c) > material layer thickness (L) > drop height (H). The EDEM simulation methodology was adopted to validate the experimental results, and the results show that there is a minimal relative error (−1% < δ < 1%) between the measured and simulated rebound heights, indicating that the established model shows a reliable prediction performance. Moreover, by comprehensively analyzing stress, strain, and energy during the collision process between rapeseed and Q235 steel, it can be concluded that the process can be divided into five stages—free fall, collision compression, collision recovery, rebound oscillation, and rebound stabilization. The maximum stress (1.19 × 10⁻² MPa) and strain (6.43 × 10⁻⁶ mm) were observed at the beginning of the collision recovery stage, which can provide some theoretical and practical basis for optimizing and designing rapeseed machines, thus achieving the goals of precise control, harvest loss reduction, and increased yields. Full article

Soil salinization severely limits plant growth and productivity. Mulberry (Morus alba L.), an economically and ecologically important tree, is widely cultivated, yet its salt-tolerance mechanisms at the seedling stage remain insufficiently understood. This study investigated the physiological and biochemical responses of two-year-old mulberry (‘Tailai Sang’) seedlings subjected to six NaCl treatments (0, 50, 100, 150, 200, and 300 mmol L⁻¹) for 28 days. Results showed that growth parameters and photosynthetic gas exchange exhibited dose-dependent declines. The reduction in net photosynthetic rate (Pn) was attributed to both stomatal limitations (decreased stomatal conductance) and non-stomatal limitations, as evidenced by a significant decrease in the maximum quantum efficiency of photosystem II (Fv/Fm) under high salinity. To cope with osmotic stress, seedlings accumulated compatible solutes, including soluble sugars, proteins, and proline. Critically, mulberry seedlings demonstrated effective ion homeostasis by sequestering Na⁺ in the roots to maintain a high K⁺/Na⁺ ratio in leaves, a mechanism that was compromised above 150 mmol L⁻¹. Concurrently, indicators of oxidative stress—malondialdehyde (MDA) and H₂O₂—rose significantly with salinity, inducing the activities of antioxidant enzymes (SOD, CAT, APX, and GR), which peaked at 150 mmol L⁻¹ before declining under extreme stress. A biomass-based LC₅₀ of 179 mmol L⁻¹ NaCl was determined. These findings elucidate that mulberry salt tolerance is a coordinated process involving three key mechanisms: osmotic adjustment, selective ion distribution, and a robust antioxidant defense system. This study establishes an indicative tolerance threshold under controlled conditions and provides a physiological basis for further field-based evaluations of ‘Tailai Sang’ mulberry for cultivation on saline soils. Full article

Lotus (Nelumbo nucifera Gaertn.) is a quintessential medicinal and edible plant, exhibiting marked differences in therapeutic effects among its various parts. The lotus seed constitutes a key component of this plant. Notably, the entire seed and the plumule display distinct medicinal properties. To investigate the “homologous plants with different effects” phenomenon in traditional Chinese medicine, this study established a Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) method. This study employed immature lotus seeds as the experimental material, diverging from the mature seeds conventionally used. Conductive double-sided tape was employed for sample preparation, and complete longitudinal sections of the seeds were obtained, followed by MALDI-MSI analysis to identify and visualize the spatial distribution of characteristic secondary metabolites within the entire seeds. The results unveiled the diversity of metabolites in lotus seeds and their differential distribution across tissues, with pronounced distinctions in the plumule. A total of 152 metabolites spanning 13 categories were identified in lotus seeds, with 134, 89, 51, and 98 metabolites discerned in the pericarp, seed coat, cotyledon, and plumule, respectively. Strikingly, young lotus seeds were devoid of liensinine/isoliensinine and neferine, the dominant alkaloids of mature lotus seed plumule, revealing an early-stage alkaloid profile that sharply contrasts with the well-documented abundance found in mature seeds and has rarely been reported. We further propose a biosynthetic pathway to explain the presence of the detected benzylisoquinoline and the absence of the undetected bisbenzylisoquinoline alkaloids in this study. These findings present the first comprehensive metabolic atlas of immature lotus seeds, systematically exposing the pronounced chemical divergence from their mature counterparts, and thus lays a metabolomic foundation for dissecting the spatiotemporal mechanisms underlying the nutritional and medicinal value of lotus seeds. Full article

Lung cancer is one of the most common cancers and the leading cause of cancer-related death worldwide. Despite advancements, the overall survival rate for lung cancer remains between 10% and 20% in most countries. However, recent progress in diagnostic tools and therapeutic strategies has led to meaningful improvements in survival outcomes, highlighting the growing importance of personalized management based on accurate disease assessment. ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) has become essential in the management of lung cancer, serving as a key imaging modality for initial diagnosis, staging, treatment response assessment, and follow-up evaluation. Recent developments in radiomics and artificial intelligence (AI), including machine learning and deep learning, have revolutionized the analysis of complex imaging data, enhancing the diagnostic and predictive capabilities of FDG PET/CT in lung cancer. However, the limitations of FDG, including its low specificity for malignancy, have driven the development of novel oncologic radiotracers. One such target is fibroblast activation protein (FAP), a type II transmembrane glycoprotein that is overexpressed in activated cancer-associated fibroblasts within the tumor microenvironment of various epithelial cancers. As a result, FAP-targeted radiopharmaceuticals represent a novel theranostic approach, offering the potential to integrate PET imaging with radioligand therapy (RLT). In this review, we provide a comprehensive overview of FDG PET/CT in lung cancer, along with recent advances in AI. Additionally, we discuss FAP-targeted radiopharmaceuticals for PET imaging and their potential application in RLT for the personalized management of lung cancer. Full article

Multimodal sentiment analysis (MSA) faces key challenges such as incomplete modality inputs, long-range temporal dependencies, and suboptimal fusion strategies. To address these, we propose MGMR-Net, a Mamba-guided multimodal reconstruction and fusion network that integrates modality-aware reconstruction with text-centric fusion within an efficient state-space modeling framework. MGMR-Net consists of two core components: the Mamba-collaborative fusion module, which utilizes a two-stage selective state-space mechanism for fine-grained cross-modal alignment and hierarchical temporal integration, and the Mamba-enhanced reconstruction module, which employs continuous-time recurrence and dynamic gating to accurately recover corrupted or missing modality features. The entire network is jointly optimized via a unified multi-task loss, enabling simultaneous learning of discriminative features for sentiment prediction and reconstructive features for modality recovery. Extensive experiments on CMU-MOSI, CMU-MOSEI, and CH-SIMS datasets demonstrate that MGMR-Net consistently outperforms several baseline methods under both complete and missing modality settings, achieving superior accuracy, robustness, and generalization. Full article

Natural fiber-based biocomposites are rapidly gaining traction in sustainable manufacturing. However, their supply chain (SC) designs at the feedstock pre-processing stage often lack robust multicriteria decision-making evaluations, which can impact downstream processes and final product quality. This case study proposes a sustainability-driven multicriteria decision-making framework for selecting pre-processing equipment configurations within a hemp-based biocomposite SC. Using a cradle-to-gate system boundary, four alternative configurations combining balers (square vs. round) and hammer mills (full-screen vs. half-screen) are evaluated. The analytical network process (ANP) model is used to evaluate alternative SC configurations while capturing the interdependencies among environmental, economic, social, and technical sustainability criteria. These criteria are further refined with the inclusion of sub-criteria, resulting in a list of 11 key performance indicators (KPIs). To evaluate ranking robustness, a non-linear programming (NLP)-based sensitivity model is developed, which minimizes the weight perturbations required to trigger rank reversals, using an IPOPT solver. The results indicated that the Half-Round setup provides the most balanced sustainability performance, while Full-Square performs best in economic and environmental terms but ranks lower socially and technically. Also, the ranking was most sensitive to the weight of the system reliability and product quality criteria, with up to a 100% shift being required to change the top choice under the ANP model, indicating strong robustness. Overall, the proposed framework enables decision-makers to incorporate uncertainty, interdependencies, and sustainability-related KPIs into the early-stage SC design of bio-based composite materials. Full article

The transgenic animals have been yielding invaluable insights into amyloid pathology by replicating the key features of Alzheimer’s disease (AD). However, there is no clear relationship between senile plaques and memory deficits. Instead, cognitive impairment and synaptic dysfunction are particularly linked to a rise in Aβ_1-42 oligomer level. Thus, injection of Aβ_1-42 oligomers into a specific brain region is considered an alternative approach to investigate the effects of increased soluble Aβ species without any plaques, offering higher controllability, credibility and validity compared to the transgenic model. The hippocampal CA1 (cornu ammonis 1) region is selectively affected in the early stage of AD and specific targeting of CA1 region directly links Aβ oligomer-related pathology with memory impairment in early AD. Next, the inhibitory avoidance (IA) task, a learning paradigm to assess the synaptic basis of CA1-dependent contextual learning, triggers training-dependent synaptic plasticity similar to in vitro HFS (high-frequency stimulation). Given its reliability in assessing contextual memory and synaptic plasticity, this task provides an effective framework for studying early stage AD-related memory deficit. Therefore, in this review, we will focus on why Aβ_1-42 oligomer injection is a valid in vivo model to investigate the early stage of AD and why dorsal CA1 region serves as a target area to understand the adverse effects of Aβ_1-42 oligomers on contextual learning through the IA task. Full article

With the accelerating globalization and rapid development of science and technology, scientific collaboration has become a key driver of knowledge production, yet its patterns vary significantly across disciplines. This study aims to explore the disciplinary differences in scholars’ scientific collaboration patterns and their underlying mechanisms. Data were collected from the China National Knowledge Infrastructure (CNKI) database, covering papers from four disciplines: mathematics, mechanical engineering, philosophy, and sociology. Using social network analysis, we examined core network metrics (degree centrality, neighbor connectivity, clustering coefficient) in collaboration networks, analyzed collaboration patterns across scholars of different academic ages, and compared the academic age distribution of collaborators and network characteristics across career stages. Key findings include the following. (1) Mechanical engineering exhibits the highest and most stable clustering coefficient (mean 0.62) across all academic ages, reflecting tight team collaboration, with degree centrality increasing fastest with academic age (3.2 times higher for senior vs. beginner scholars), driven by its reliance on experimental resources and skill division. (2) Philosophy shows high degree centrality in early career stages (mean 0.38 for beginners) but a sharp decline in clustering coefficient in senior stages (from 0.42 to 0.17), indicating broad early collaboration but loose later ties due to individualized knowledge production. (3) Mathematics scholars prefer collaborating with high-centrality peers (higher neighbor connectivity, mean 0.51), while sociology shows more inclusive collaboration with dispersed partner centrality. Full article

The ongoing advancement of urbanization has significantly amplified its impacts on the water environment. Understanding the coupling relationships between urbanization and the water environment (UAWE) is crucial for Chinese policymakers aiming to promote sustainable urban development. In this study, a comprehensive UAWE evaluation model was developed to examine the development trajectories in Neijiang City from 2012 to 2022. Methodologically, a comprehensive evaluation approach was applied to assess urbanization and water resource trends over this period, followed by the development of a Coupling Coordination Degree Model (CCDM) to quantify their synergistic relationship. The results showed that the coupling between the comprehensive urbanization index and the water environment system evolved over time, as reflected in the following key findings: (1) Neijiang underwent three distinct stages from 2012 to 2022 in terms of coupling and coordination between urbanization and the water environment: Basic Coordination (2012–2015), Good Coordination (2016–2020), and Excellent Coordination (2020–2022). (2) Urbanization exerted varying impacts on subsystems of the water environment, with the pressure-response subsystems exhibiting marked volatility from 2012 to 2022. The impact intensity followed the order spatial urbanization > economic urbanization > social urbanization > population urbanization. These findings offer valuable theoretical and practical insights for aligning urban sustainability goals with effective water environment protection measures. This study provides essential guidance for policymakers in Neijiang and similar regions, enabling the development of tailored strategies for sustainable urbanization and enhanced water management. Full article

Triple-negative breast cancer (TNBC) is a clinically and molecularly heterogeneous subtype defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. In this study, tumor specimens from 104 TNBC patients were analyzed to characterize molecular and clinicopathological features and to assess the expression and therapeutic potential of four key surface markers: epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule (EpCAM), tissue factor (TF), and trophoblast cell surface antigen (TROP2). Multiplex immunofluorescence (mIF) demonstrated elevated EGFR and TROP2 expression in the majority of samples. Significant positive correlations were observed between EGFR and TF, as well as between TROP2 and both TF and EpCAM. Expression analyses revealed increased EGFR and TF levels with advancing tumor stage, whereas EpCAM expression declined in advanced-stage tumors. TROP2 and TF expression were significantly elevated in higher-grade tumors. Additionally, EGFR and EpCAM levels were significantly higher in patients with elevated Ki-67 indices. Binding specificity assays using single-chain variable fragment (scFv-SNAP) fusion proteins confirmed robust targeting efficacy, particularly for EGFR and TROP2. These findings underscore the therapeutic relevance of EGFR and TROP2 as potential biomarkers and targets in TNBC. Full article

This study presents the first investigation into the application of ultrasonic vibration-assisted electrical discharge machining (UV-EDM) using graphite electrodes for external cylindrical surface machining—an essential surface in the production of tablet punches and sheet metal-forming dies. A custom ultrasonic horn was designed and fabricated using 90CrSi material to operate effectively at a resonant frequency of 20 kHz, ensuring stable vibration transmission throughout the machining process. A Box–Behnken experimental design was employed to explore the effects of five process parameters—vibration amplitude (A), pulse-on time (Ton), pulse-off time (Toff), discharge current (Ip), and servo voltage (SV)—on two key performance indicators: material removal rate (MRR) and surface roughness (Ra). The optimization process was conducted in two stages: single-objective analysis to maximize MRR while ensuring Ra < 4 µm, followed by a hybrid multi-objective approach combining NSGA-II and the Analytic Hierarchy Process (AHP). The optimal solution achieved a high MRR of 9.28 g/h while maintaining Ra below the critical surface finish threshold, thus meeting the practical requirements for punch surface quality. The findings confirm the effectiveness of the proposed horn design and hybrid optimization strategy, offering a new direction for enhancing productivity and surface integrity in cylindrical EDM applications using graphite electrodes. Full article

Background: Faced with the profound impact of major infectious diseases on public life and economic development, humans have long sought to understand disease transmission and intervention strategies. To better explore the impact of individuals’ different coping behaviors—triggered by changes in their psychological security due to public information and external environmental changes—on the spread to infectious diseases, the model will place greater emphasis on quantifying psychological factors to make it more aligned with real-world situations. Methods: To better understand the interplay between information dissemination and disease transmission, we propose a two-layer network model that incorporates psychological safety factors. Results: Our model reveals key insights into disease transmission dynamics: (1) active defense behaviors help reduce both disease spread and information diffusion; (2) passive resistance behaviors expand disease transmission and may trigger recurrence but enhance information spread; (3) high-timeliness, low-fuzziness information reduces the peak of the initial infection but does not significantly curb overall disease spread, and the rapid dissemination of disease-related information is most effective in limiting the early stages of transmission; and (4) community structures in information networks can effectively curb the spread of infectious diseases. Conclusions: These findings offer valuable theoretical support for public health strategies and disease prevention after government information release. Full article