Search Results (829)

Background/Objectives: Neovascular age-related macular degeneration (nAMD) poses a serious threat to the eyesight of older adults, representing a leading cause of irreversible vision loss. Anti-vascular endothelial growth factor (anti-VEGF) treatments are effective but require repeated intraocular injections and show poor responses in some patients. CGK012 is a novel derivative of decursin that inhibits the Wnt/β-catenin pathway. This study aimed to elucidate the mode of action of CGK012 and examine its therapeutic effects. Methods: We performed in vitro cellular studies in a retinal pigment epithelial (RPE) cell line (ARPE-19) and human umbilical vein endothelial cells (HUVECs). We examined the in vivo efficacy of CGK012-loaded implants in laser-induced choroidal neovascularization (CNV) rabbit models. We also determined the implants’ in vitro dissolution, intraocular release, and disposition characteristics. Results: CGK012 decreased angiogenic/proinflammatory factor expression and suppressed the epithelial–mesenchymal transition (EMT) in RPE cells by promoting intracellular β-catenin degradation. Additionally, it repressed the expression of cyclin D1 and c-myc, downstream target genes of β-catenin, and inhibited HUVEC capillary tube formation. CGK012-loaded poly (lactic-co-glycolic acid) (PLGA) intravitreal implants significantly reduced vascular leakage in a laser-induced CNV rabbit model. Notably, CGK012 released from the implant was highly permeable to retina/choroid tissue and downregulated β-catenin, angiogenic/inflammatory factors, and vimentin in the rabbit model. The CGK012 concentration reached a plateau at 28–42 days in the vitreous humor and decayed with a half-life of 14 days without systemic exposure. Conclusions: Our findings demonstrate that CGK012 implants prevent choroidal neovascularization through the Wnt/β-catenin pathway suppression and produce high concentrations of CGK012 in the posterior eye segment with prolonged release. Thus, these implants provide more therapeutic choices for nAMD treatment. Full article

Objectives: Burn being a major traumatic issue worldwide impacts millions of lives annually. Herein, a novel xanthan dialdehyde/sodium alginate/copper-doped mesoporous bioactive glass nanoparticle (XDA/Na-ALG/Cu-MBGN) hydrogel is presented in this study. Methods: The hydrogel was fabricated by a casting method, followed by its characterization in terms of its morphology, surface topography, and in vitro biochemical and physical interactions. Results: Scanning electron microscopy images revealed the rough surface of the hydrogel, ideal for cell attachment and proliferation. The nanoporous structure revealed by BET enabled it to hold moisture for an extended span. The nanopores were developed because of the ether linkage developed between XDA and Na-ALG, as evident from Fourier Transform Infrared Spectroscopy. The loading of Cu-MBGNs was also confirmed by FTIR. The release of copper ions was sustained throughout the 7 days, and it is accounting for about 22 µg/mL in 330 h, which follows the degradation kinetics of XDA/Na-ALG/Cu-MBGN hydrogels. The released copper ions promoted angiogenesis, as confirmed by the enhanced release of vascular endothelial growth factor (VEGF) for the XDA/Na-ALG/Cu-MBGN hydrogel (275 ng/mL) in comparison to 200 ng/mL of the bare TCP. The hydrogel, despite being bactericidal against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) did not show toxicity towards human dermal fibroblasts confirmed via a Water-Soluble Tetrazolium 8 assay. Conclusions: Hence, the developed XDA/Na-ALG/Cu-MBGN hydrogel possesses potential to be investigated further in terms of in vivo interactions. Full article

Heavy metal contamination in agricultural soils poses serious threats to food safety, ecosystem integrity, and public health. This study investigates the concentrations, ecological risks, and human health impacts of nine heavy metals Cr, Mn, Co, Ni, Cu, Zn, Pb, As, and V in homestead agricultural soils collected from two depths, surface (0–20 cm) and subsurface (21–50 cm), across industrial and non-industrial regions of Bangladesh, using inductively coupled plasma mass spectrometry (ICP-MS). Results revealed that surface soils from industrial areas exhibited the highest metal concentrations in order of Mn > Zn > Cr > Pb > V > Ni > Cu > As > Co. However, maximum As levels were detected in non-industrial areas, suggesting combined influences of local geology, intensive pesticide application, and prolonged irrigation with As-contaminated groundwater. Elevated concentrations in surface soils indicate recent contamination with limited downward migration. Multivariate statistical analyses indicated that industrial and urban activities are the major sources of contamination, whereas Mn remains primarily geogenic, controlled by natural soil forming processes. Contamination factor (CF) and pollution load index (PLI) analyses identified Pb and As as the principal pollutants, with hotspots in Nairadi, Majhipara (Savar), Gazipur sadar, and Chorkhai (Mymensingh). Ecological risk (ER) assessment highlighted As and Pb as the dominant environmental stressors, though overall risk remained low. Human health risk analysis showed that ingestion is the primary exposure pathway, with children being more susceptible than adults. Although the hazard index (HI) values were within the acceptable safety limits, the estimated carcinogenic risks for As and Cr exceeded the USEPA thresholds, indicating potential long term health concerns. Therefore, the cumulative carcinogenic risk (CCR) results demonstrate that As is the primary driver of lifetime carcinogenic risk in homestead soils, followed by Cr, while contributions from other metals are minimal. These findings emphasize the urgent need for continuous monitoring, improved industrial waste management, and targeted mitigation strategies to ensure safe food production, a cleaner environment, and better public health. Full article

Tendon injuries present significant clinical challenges due to limited intrinsic healing and complex pathological mechanisms. Here, we developed a novel 3D bioprinted methacrylated type I collagen (ColMA) scaffold integrated with Growth Differentiation Factor-5 (GDF-5)-loaded Poly (lactic-co-glycolic acid) (PLGA) nanoparticles and dynamically cultured it under perfusion to establish a tenogenic microenvironment in vitro. Pathological human Tendon Stem/Progenitor Cells (hTSPCs) derived from tendinopathic surgical explants were encapsulated to investigate their impaired extracellular matrix (ECM) deposition and associated pro-inflammatory signaling. GDF-5-loaded nanoparticles (average diameter 140 ± 40 nm) were fabricated via microfluidic-assisted nanoprecipitation and homogeneously incorporated within the ColMA synthetic ECM to enable sustained growth factor release. Continuous perfusion culture (1 mL/min) ensured efficient mass transfer and supported cell viability above 70% over 21 days. Pathological hTSPCs exhibited impaired ECM remodeling, characterized by the absence of type I collagen and a 2.56-fold increase in type III collagen at day 7, indicative of a fibrotic-like phenotype. Western blot densitometry demonstrated a 5.31-fold elevation in secreted tenomodulin at day 14, while ECM analysis verified a type III to type I collagen ratio of 4.5. In addition, a markedly pro-inflammatory cytokine profile was observed, with elevated secretion of interleukin-6 (IL-6) and interleukin-8 (IL-8) from day 7 onward, consistent with the chronic inflammatory status of cells derived from pathological tendon tissues. This modular 3D platform represents a robust in vitro model for mechanistic studies and the advancement of personalized regenerative strategies targeting chronic tendon disorders. Full article

Craniofacial bone defects of critical size, caused by trauma, tumors, infections, or congenital maldevelopment, represent a major challenge in plastic and reconstructive surgery. Autologous bone grafting is considered the gold standard, but limitations such as donor site morbidity and limited availability have prompted the development of artificial bone tissue engineering scaffolds. In recent years, bioactive scaffolds have been increasingly utilized in favor of inert biomaterials due to their immunomodulation and osteoinduction capabilities. This review methodically summarizes loading strategies for the functionalization of scaffolds with bioactive components, including cell regulatory factors, drugs, ions, stem cells, exosomes, and components derived from human tissues or cells to promote bone regeneration. The following mechanisms are involved: (1) the polarization of macrophages (M1-M2 transition), (2) the dynamic regulation of bone metabolism, and (3) the coupling of osteogenesis and angiogenesis. This review focuses on innovative delivery systems, such as 3D-printed scaffolds, nanocomposites and so on, that enable spatiotemporal control of bioactive cargo release. These address key challenges, such as infection resistance, vascularization, and mechanical stability in the process of bone regeneration. In addition, the article discusses emerging technologies, including stem cells and exosome-based acellular therapies, which demonstrate potential for personalized bone regeneration. This review integrates immunology, materials science, and clinical needs, providing a roadmap for the design of next-generation bone tissue engineering scaffolds to overcome critical-sized bone defects. Full article

In recent decades, the suspended sediment load (SSL) of many rivers around the world has shown a significant decreasing trend, which is particularly prominent in large river basins such as the Yangtze River and the Yellow River. One of the key challenges currently faced is how to quantitatively determine the relative influence of the dominant factors on the basis of systematically assessing the changing trend of SSL. This study takes the upper reaches of the Yangtze River as the research object. Based on the observation data from representative hydrological stations during 1966–2024, it systematically analyzes the interannual variation trend of SSL in different sections of the study river reach, identifies several mutation points, and divides the SSL change process into a baseline period, change period I, and change period II. Using the SCRCQ (slope change ratio of cumulative quantity) method, the study finds that the contribution ratio of human activities to the reduction of SSL in different sections of the study river reach ranges from 87.5% to 111.9%, the contribution ratio of precipitation change ranges from −14.3% to 12.4%, and the contribution ratio of evapotranspiration change ranges from −0.1% to 0.6%. For the entire upper Yangtze River basin, the contribution ratios of human activities to the reduction of SSL during change period I and change period II are 87.5% and 95.1%, respectively, while those of climate change are 12.4% and 4.9%, respectively. Human activities play an absolutely dominant role in the reduction of SSL in the upper Yangtze River. The results of this study can provide guidance for the scientific management of river reaches with concentrated large-scale reservoirs in the upper Yangtze River and also offer references for the formulation of management measures for similar rivers worldwide. Full article

Exploring the spatiotemporal pattern of water quality and identifying pollution sources is crucial for achieving precise management of reservoir watersheds. This study is based on monthly water quality data from 9 monitoring stations in the upstream watershed of Guanting Reservoir in 2024, combined with an improved water quality index method (WQI) and multivariate statistical analysis (clustering, discrimination, principal component and factor analysis), to reveal the spatiotemporal variation characteristics of water quality and pollution sources. The results show (1) significant spatiotemporal heterogeneity. In terms of time, the water quality is worst during the summer rainy season (June August), indicating that the pollution load input from surface runoff exceeds the dilution effect of rainfall. In terms of space, the water quality deteriorates significantly downstream along the river network, with the most prominent pollution occurring in the entrance area. (2) The results also show clear identification of key indicators and dominant pollution sources. Discriminant analysis shows that BOD₅ and DO are key indicators for distinguishing rainy and dry seasons, while TN, TP, COD, COD_Mn, and F can effectively distinguish spatial clusters. Factor analysis further revealed that organic pollution (originating from domestic and industrial wastewater) and nutrient pollution (mainly from agricultural non-point sources) are the dominant factors. This study confirms that pollution input during rainfall is the primary driving factor for water quality deterioration, and human activities have led to the cumulative effect of pollutants along the river network. Based on this suggestion, differentiated and precise governance strategies should be implemented according to the spatiotemporal differentiation characteristics to improve the water environment quality of the upstream watershed of Guanting Reservoir. Full article

Background: Chronic wounds, especially in diabetic patients, pose a significant clinical challenge due to current treatment limitations and an increasingly affected population. A major issue is the stalled inflammatory phase, which prevents proper healing. This study developed a novel co-delivery system to address the deficiency of growth factors and persistent inflammation in chronic wounds. Methods: Gelatin nanoparticles (NPs) were synthesized to carry curcumin, an anti-inflammatory compound. These curcumin-loaded NPs (NP/Curc) were then incorporated into gelatin methacrylate (GelMA) hydrogels to form a hierarchical delivery construct, nanoparticles encased within a hydrogel. These hydrogels were then cryogenically milled into microparticles (MPs) to carry human mesenchymal stem cells (hMSCs). The viability and growth of hMSCs on the surface of curcumin-loaded MPs were evaluated. The release of curcumin from various MP configurations was analyzed. The anti-inflammatory effects of the MPs were assessed by measuring pro-inflammatory cytokine expression in human monocyte THP-1 cells. Results: Curcumin directly loaded into hydrogels showed a rapid burst release within three days. In contrast, NP/Curc had a more sustained release profile. Curcumin incorporation did not adversely affect the cell-carrier functions of MPs. Conditioned media from hMSCs cultured on the plain MPs demonstrated anti-inflammatory effects in THP-1 cells. Low doses of curcumin released from the MPs also showed anti-inflammatory activity. The combination of hMSCs and curcumin exhibited an additive effect in reducing IL-8 expression by 4× in THP-1 cells. Conclusions: This study demonstrates the feasibility of co-delivering cells and curcumin without compromising the cell viability of hMSCs. Using gelatin nanoparticles as a carrier prolongs curcumin release, offering a sustained therapeutic effect. This strategy of hierarchical delivery of curcumin and co-delivery of cells represents a promising approach for treating chronic wounds by simultaneously providing growth factors and reducing inflammation. Full article

The development of advanced delivery systems for bioactive factors is a critical focus in regenerative medicine and tissue engineering. In this study, we present a waterborne polyurethane (WPU)-based scaffold fabricated through a fully aqueous electrospinning process, providing a solvent-free and green method for delivering secretome derived from human mesenchymal stromal cells (MSCs). We optimized the electrospinning parameters to enable efficient secretome incorporation while preserving fiber morphology, sterility, and biocompatibility. The resulting membranes exhibited a uniform nanofibrous architecture, supported high cell viability, and demonstrated effective secretome loading and release, detected following release of vascular endothelial growth factor (VEGF)-A over 24 h. Overall, our findings highlight the potential of WPU nanofibrous scaffolds as sustainable and functional platforms for the delivery of MSC-derived bioactive factors in biomedical applications. Full article

The rapid advancement of flexible electronics has propelled the development of lightweight, wearable piezoresistive sensors that integrate high sensitivity, excellent mechanical properties, and multifunctionality, making them a research hotspot. This work presents a flexible and lightweight multifunctional polyvinyl alcohol (PVA) composite hydrogel film, which is constructed based on a synergistic conductive network of cuttlefish ink-derived carbon nanospheres (CNPs) and polypyrrole (PPy). Within this composite, the CNPs and PPy form an interpenetrating conductive network throughout the PVA matrix, where PPy effectively suppresses the agglomeration of CNPs, thereby significantly enhancing the electron transport efficiency. This unique structure endows the material with improved flame retardancy and hydrophobicity while maintaining its lightweight characteristic. Consequently, the sensor demonstrates fast response (64 ms) and recovery times (66 ms) and a high sensitivity factor of 4.34 kPa⁻¹ within a pressure range of 11.2–16.8 kPa. Excellent stability is retained after nearly 6000 loading–unloading cycles, primarily attributed to the efficient response of the contact points and conductive pathways within the synergistic network under stress. Furthermore, this flexible sensor can not only reliably monitor human physiological activities (such as finger joint bending and facial expression changes) but also generate distinct current responses to subtle mouse-clicking actions, enabling tactile handwriting input. This study provides a novel strategy for constructing high-performance sensing materials by utilizing natural biomass-derived carbon materials and conductive polymers, highlighting the significant application potential of such lightweight, multifunctional hydrogel films in next-generation flexible electronic devices. Full article

Despite the growing use of Explainable Artificial Intelligence (XAI) in energy time-series forecasting, a systematic evaluation of explanation quality remains limited. This systematic review analyzes 50 peer-reviewed studies (2020–2025) applying XAI to load, price, or renewable generation forecasting. Using a PRISMA-inspired protocol, we introduce a dual-axis taxonomy and a four-factor framework covering global transparency, local fidelity, user relevance, and operational viability to structure our qualitative synthesis. Our analysis reveals that XAI application is not uniform but follows three distinct, domain-specific paradigms: a user-centric approach in load forecasting, a risk management approach in price forecasting, and a physics-informed approach in generation forecasting. Post hoc methods, particularly SHAP, dominate the literature (62% of studies), while rigorous testing of explanation robustness and the reporting of computational overhead (23% of studies) remain critical gaps. We identify key research directions, including the need for standardized robustness testing and human-centered design, and provide actionable guidelines for practitioners. Full article

Wind-induced acceleration represents one of the main challenges in the dynamic behavior of tall buildings. Its estimation can be carried out through experimental wind tunnel tests or using the analytical expressions proposed in various international codes and standards. However, the explicit consideration of uncertainty in structural dynamic properties, wind characteristics, and human-perceived response is limited or nonexistent in most standards. Slender structures like tall buildings can experience excessive acceleration due to wind loading, which can impact the activities of the buildings’ users. To prevent excessive wind-induced vibration, some international codes require that the serviceability limit state, in terms of acceleration, is satisfied. These serviceability limit states require that the wind-induced acceleration is less than or equal to a predefined value, which is taken from perception curves that are developed based on perceived vibration alone. The main objective of this work is to develop acceleration factors for across-wind and torsional acceleration that are calibrated for the selected targeted probability of perception levels by considering the uncertainty in the structural dynamic characteristics and wind characteristics, as well as in the human perception of motion. The acceleration factors are incorporated in a simple-to-use procedure to evaluate the wind-induced acceleration in tall buildings. A numerical example is provided to illustrate the use of the proposed acceleration factors. Full article

Hypertension is a leading risk factor for cardiovascular disease and is associated with maladaptive cardiac remodeling, including hypertrophy and fibrosis. The roles of the receptor for advanced glycation end-products (RAGE) and the small GTPase Rap1a in angiotensin II (AngII)-induced remodeling remain unclear. This study examined how RAGE and Rap1a influence cardiac responses to AngII using wild-type (WT), RAGE knockout (RAGE KO), and Rap1a knockout (RapKO) mice. Cardiac structure and function were evaluated following AngII infusion. RapKO mice were protected from AngII-induced hypertrophy, whereas RAGE KO mice exhibited altered remodeling patterns. AngII consistently increased left ventricular wall thickness across all genotypes, indicating that structural remodeling is primarily treatment-driven. Measures of cardiac output and stroke volume also changed significantly with AngII, suggesting hemodynamic load as a key driver of functional adaptation. In contrast, diastolic functional parameters were genotype-dependent and remained stable with AngII exposure, demonstrating an intrinsic influence of RAGE and Rap1a on myocardial relaxation. These findings highlight distinct roles for RAGE and Rap1a in modulating hypertensive cardiac remodeling and may parallel human hypertensive heart disease, where increased RAGE and Rap1a expression associate with fibrosis and impaired relaxation. Targeting the crosstalk between the RAGE-AT1R axis and the cAMP-EPAC-Rap1a pathway may offer therapeutic potential to reduce adverse cardiac remodeling in hypertension. Full article

In psychology, small sample sizes are a frequent challenge—particularly when studying specific expert populations or using complex and cost-intensive methods like human scoring of creative answers—as they reduce statistical power, bias results, and limit generalizability. They also hinder the use of frequentist confirmatory factor analysis (CFA), which depends on larger samples for reliable estimation. Problems such as non-convergence, inadmissible parameters, and poor model fit are more likely. In contrast, Bayesian methods offer a robust alternative, being less sensitive to sample size and allowing the integration of prior knowledge through parameter priors. In the present study, we introduce small-sample-size structural equation modeling to creativity research by investigating the relationship between creative fluency and nested creative cleverness with right-wing authoritarianism, starting with a sample size of N = 198. We compare the stability of results in frequentist and Bayesian SEM while gradually reducing the sample by n = 25. We find that common frequentist fit indexes degrade below N = 100, while Bayesian multivariate Rhat values indicate stable convergence down to N = 50. Standard errors for fluency loadings inflate 40–50% faster in frequentist SEM compared to Bayesian estimation, and regression coefficients linking RWA to cleverness remain significant across all reductions. Based on these findings, we discuss (1) the critical role of Bayesian priors in stabilizing small-sample SEM, (2) the robustness of the RWA-cleverness relationship despite sample constraints, and (3) practical guidelines for minimum sample sizes in bifactor modeling. Full article

There is a critical demand for flexible resistive sensors that combine high sensitivity with a wide linear range, fast response speed, and excellent long-term stability. This study presents the development of a high-performance resistive flexible sensor utilizing graphene-coated iron nanowires (Fe NWs@Graphene) as conductive fillers within a polyurethane sponge (PUS) substrate. The sensor was constructed with a sandwich-like structure, consisting of Fe NWs@Graphene-impregnated PUS as the sensing layer, encapsulated by polydimethylsiloxane (PDMS) for protection. The Fe NWs were synthesized via a chemical reduction process employing an external magnetic field. Subsequent chemical vapor deposition enabled uniform graphene coating on the surface of Fe NWs. Systematic performance assessments demonstrated that the Fe NWs@Graphene flexible sensor exhibits a gauge factor (GF) of 14.5 within a 0–100% strain range, representing a 71% improvement over previously reported Fe NW-based strain sensors, along with excellent linearity (R² = 0.994). The sensor also showed rapid response times (113 ms for loading and 97 ms for unloading) and outstanding cyclic stability over 3000 stretching cycles at 50% strain. These enhancements are attributed to the synergistic effects between Fe NWs and graphene: the graphene shell effectively protects the Fe NW core against oxidation, thereby improving stability, and facilitates efficient charge transport, while the Fe NWs serve as bridging agents that improve both mechanical integrity and electrical percolation. In addition, application tests simulating human motion detection confirmed the sensor’s ability to accurately capture muscle-induced strain signals with high repeatability. The results underscore the feasibility of Fe NWs@Graphene as conductive fillers for high-sensitivity, wide-range, and stable flexible sensors, highlighting the potential in wearable electronics and human–machine interaction systems. Full article