Search Results (1,194)

Alzheimer’s disease (AD), the most frequent neurodegenerative disorder worldwide, is characterized by two key pathological features: extracellular amyloid beta plaques and intracellular highly phosphorylated tau protein aggregates known as neurofibrillary tangles. While in the last decades intensive research related to anti-amyloid disease-modifying therapies for AD was conducted, there has been less interest in treatments targeting tau protein. However, this paradigm is slowly changing, as recent studies have shown the increasing importance of tau protein in the onset and evolution of AD. In this context, this review aims to offer a practical overview of currently available therapies targeting tau protein and future research directions. The first part of the manuscript highlights the pathophysiological basics of tau protein aggregation and tau-related kinase dysregulations, considering their role in physiological versus AD conditions. Subsequently, the most relevant classes of drugs modulating tau protein formation, aggregation, and post-translational modifications are presented, with appropriate examples from clinical trials. Finally, unexplored research directions regarding tau-targeting therapies are discussed, with active and passive immunotherapies a promising research direction. Therapies targeting tau protein are a valuable treatment modality in AD, with current drug classes expected to diversify soon. Full article

Chronic kidney disease of unknown origin (CKDu) is a public health concern, particularly in agricultural communities, with multiple environmental exposures hypothesized as potential contributors. This study employed a targeted exposure assessment using personal silicone wristbands to characterize chemical exposures among women living and working in CKDu-affected regions of Guatemala. Participants wore wristbands for seven days, passively sampling air and dermal exposures. Overall, 45 wristbands were collected from 37 female participants (19 sugarcane workers and 18 community members). Of the 1530 chemicals measured using a single semi-quantitative method, 103 were detected, with an average of 27 chemicals per wristband (range: 16–40). Polycyclic aromatic hydrocarbon (PAH) levels were higher in community members’ wristbands, whereas workers exhibited higher exposure to pesticides (i.e., pendimethalin and fipronil). Workers had worse kidney function compared to community members, with almost half of the workers having an estimated glomerular filtration rate, eGFR, <90 mL/min/1.73 m². Correlations were observed between kidney function markers and specific chemicals, with the strongest correlation between albumin-to-creatinine ratio and pyrene levels (ρ = 0.57, p < 0.01) among workers. Women in agricultural regions of Guatemala experience widespread exposure to diverse environmental chemicals, some of which may contribute to kidney function decline. Full article

The rational design of advanced functional materials with tailored fluorescence hinges on a profound understanding of the complex interplay between a molecule’s intrinsic structure and its local solid-state environment. This work systematically investigates these factors by employing a dual approach that combines targeted molecular synthesis with the subsequent modulation of the fluorophore’s properties within polymer matrices. First, a series of phenylhydrazone derivatives was synthesized, providing compounds with intense, solid-state fluorescence in the blue spectrum (421–494 nm). It was demonstrated that their photophysical properties were intricately linked to the substituent’s nature, which simultaneously modulated their intramolecular electron density and conformational rigidity while also governing their specific intermolecular packing in the solid state. Subsequently, we investigated the role of the supramolecular environment by embedding two fluorophores with distinct electronic profiles into electrospun poly (N-vinylpyrrolidone) (PVP) and polystyrene (PS) matrices. Our results reveal that the polymer matrix is not a passive host but an active component; it governs dye aggregation, induces significant blue shifts, and most critically, can impart exceptional thermal stability. Specifically, the PVP matrix shielded the embedded dyes from thermal quenching, maintaining robust fluorescence up to 100 °C. By combining molecular-level synthesis with matrix-level engineering, this work demonstrates a powerful strategy for the rational design of emissive materials, where properties like color and operational stability can be deliberately tuned for demanding applications in optoelectronics and sensing. Full article

Effective intracellular delivery for ovarian cancer therapy remains a significant challenge. We present chrysin-loaded p(MMA-co-DMAEMA)-b-(OEGMA-co-DMA), PMOD-Chr, a nanoparticle platform precisely engineered via RAFT polymerization for advanced therapeutic delivery. This multi-functional platform features a hydrophobic p(MMA) core encapsulating chrysin (Chr), a pH-responsive p(DMAEMA) segment for endosomal escape, and a hydrophilic OEGMA (Oligo(ethylene glycol) methyl ether methacrylate) shell functionalized for enhanced cellular affinity and systemic stability. The combination of OEGMA and DMA (Dopamine methacrylamide) block facilitates passive targeting of ovarian cancer cells, enhancing internalization. Nanoparticles prepared via the nanoprecipitation method exhibited ~220 nm, demonstrating effective size modulation along with high homogeneity and spherical morphology. In A2780 and OVCAR3 ovarian cancer cells, PMOD-Chr demonstrated significantly enhanced cytotoxicity, substantially lowering the effective IC₅₀ dose of Chr. Mechanistically, PMOD-Chr induced a potent G2/M cell cycle arrest, driven by the upregulation of the CDK1/Cyclin B1 complex. Furthermore, the formulation potently triggered programmed cell death by concurrently activating both the intrinsic apoptotic pathway, evidenced by the modulation of Bax, Bcl2, and caspase 9, and the extrinsic pathway involving caspase 8. These findings emphasize that precision engineering via RAFT polymerization enables the creation of sophisticated, multi-stage nanomedicines that effectively overcome key delivery barriers, offering a highly promising targeted strategy for ovarian cancer. Full article

Post-consumer plastic waste poses increasing challenges in urban areas, where recycling heavily relies on consumer cooperation. In Japan, two recycling routes for post-consumer plastic waste from households exist, the municipal recycling route and the retailer recycling route, with the latter requiring more voluntary effort. This study aims to explore the diversity of consumers’ cooperative behaviors in Japan’s post-consumer plastic waste recycling system, with a focus on the retailer route. We conducted an online survey with 758 respondents from Sendai, Kawasaki, and Kyoto in urban Japan, using a structured questionnaire based on the knowledge–attitude–practice (KAP) framework. K-means clustering was conducted to identify behaviorally distinct consumer groups. Three clusters were revealed: Fully Engaged Consumers, Knowledge-Driven Consumers, and Passively Engaged Consumers. These groups exhibited distinct differences in cooperative recycling behaviors and socio-demographic characteristics. Our findings demonstrate the heterogeneity of consumer cooperation and underscore the importance of targeted strategies. By focusing on the retailer recycling route and consumer segmentation, this study addresses key gaps in Japan’s research on urban plastic waste. The results provide a theoretical and empirical foundation for differentiated policy-making, ultimately supporting the transition to a more sustainable and circular economy in post-consumer plastic waste recycling in urban Japan. Full article

The self-starting capability of straight-bladed H-type Darrieus Vertical Axis Wind Turbines (VAWTs) remains a major constraint for deployment, particularly in urban, low speed, and turbulent environments. We conducted a systematic review of technological strategies to improve self-starting, grouped into five categories: (1) aerodynamic airfoil design, (2) rotor configuration, (3) passive flow control, (4) active flow control, and (5) incident flow augmentation. Searches in Scopus and IEEE Xplore (last search 20 August 2025) covered the period from 2019 to 2026 and included peer-reviewed journal articles in English reporting experimental or numerical interventions on H-type Darrieus VAWTs with at least one start-up metric. From 1212 records, 53 studies met the eligibility after title/abstract screening and full-text assessment. Data were synthesized qualitatively using a comparative thematic approach, highlighting design parameters, operating conditions, and performance metrics (torque and power coefficients) during start-up. Quantitatively, studies reported typical start-up torque gains of 20–30% for airfoil optimization and passive devices, about 25% for incident-flow augmentation, and larger but less certain improvements (around 30%) for active control. Among the strategies, airfoil optimization and passive devices consistently improved start-up torque at low TSR with minimal added systems; rotor-configuration tuning and incident-flow devices further reduced start-up time where structural or siting constraints allowed; and active control showed the largest laboratory gains but with uncertain regarding energy and durability. However, limitations included heterogeneity in designs and metrics, predominance of 2D-Computational Fluid Dynamics (CFDs), and limited 3D/field validation restricted quantitative pooling. Risk of bias was assessed using an ad hoc matrix; overall certainty was rated as low to moderate due to limited validation and inconsistent uncertainty reporting. In conclusions, no single solution is universally optimal; hybrid strategies, combining optimized airfoils with targeted passive or active control, appear most promising. Future work should standardize start-up metrics, adopt validated 3D Fluid–Structure Interaction (FSI) models, and expand wind-tunnel/field trials. Full article

As the next generation of time–space infrastructure, low-earth-orbit navigation augmentation (LEO-NA) technology has become a hot research topic, since it can overcome the vulnerabilities and limitations of global navigation satellite systems (GNSSs). Meanwhile, a LEO-NA signal can serve as a better cooperative illuminator to build more powerful passive radar (PR). This paper proposes and investigates a new and promising PR system, LEO-NA signal-based PR (LNAS-PR), which utilizes LEO-NA signals as the illuminator and utilizes an unmanned aerial vehicle (UAV) to carry the receiver. Taking advantage of higher landing power and global coverage, LNAS-PR can be used to detect maritime targets with benefits of low cost and high efficiency. However, new technical challenges of information capture and processing need to be dealt with. Therefore, this paper presents the system model, signal model, and performance analyses within a maritime monitoring scenario, providing a foundation for future in-depth research. Full article

Alzheimer’s disease is characterized by progressive cognitive decline associated with oxidative stress, neuroinflammation, and impaired neurotrophic signaling. Sulforaphane, a bioactive compound found in broccoli, has demonstrated neuroprotective effects by activating NRF2 and inhibiting NF-κB. However, the efficacy of whole-food-derived sulforaphane remains unclear. This study evaluated the neuroprotective potential of broccoli sprout extract using a scopolamine-induced mouse model of memory impairment. Mice were orally administered broccoli sprout extract once daily at doses of 100 mg/kg or 200 mg/kg for four weeks prior to behavioral and biochemical assessments. Treatment with broccoli sprout extract significantly improved scopolamine-induced deficits in long-term memory, as determined by the passive avoidance test. The spatial working memory remained unaffected. High doses of broccoli sprout extract restored hippocampal brain-derived neurotrophic factor levels and reduced cortical lipid peroxidation, suggesting antioxidant and neurotrophic benefits. Additionally, the low dose preserved striatal choline acetyltransferase expression and reduced systemic tumor necrosis factor-alpha and hippocampal cyclooxygenase-2 levels, indicating its anti-inflammatory and cholinergic protective effects. No significant changes in acetylcholinesterase activity or glutathione levels were observed. Overall, these results imply that broccoli sprout extract has multi-targeted neuroprotective effects, possibly involving redox and inflammatory regulation. Therefore, it may be a safe dietary strategy to support cognition in neurodegenerative conditions. Full article

Heatwaves are increasing in frequency and intensity owing to climate change, posing severe health risks to urban populations, particularly vulnerable groups. This study investigates public perceptions, adaptive behavior, and policy awareness regarding extreme heat in Gwangju Metropolitan City, South Korea, a heat-prone urban area. Using a mixed-methods approach, we analyzed primary survey data from 814 residents and secondary data from the 2020 Gwangju Citizen Heatwave Awareness Survey. Statistical analyses, including chi-squared and t-tests, examined differences across socioeconomic age groups. Results indicate that while general awareness of heatwave risks is high, low-income residents exhibit lower perceived severity, limited access to mechanical cooling, and greater reliance on passive avoidance behaviors. Awareness and use of municipal cooling shelters were low, with satisfaction hindered by concerns over accessibility, cleanliness, and operational hours. Television and emergency text alerts were the main information channels; however, trust and perceived usefulness were limited. Policy recommendations include spatially targeted shelter placement informed by vulnerability mapping, improved operational standards, diversified risk communication, and enhanced community engagement. This study underscores the importance of equity-driven adaptation strategies and provides practical insights for global municipalities facing similar climate-related heat risks. Full article

Heat shock proteins (HSPs), a family of proteins including HSP27, HSP40, HSP60, HSP70, and HSP90, play critical roles in cellular processes and are often dysregulated in cancer. Heat Shock Factor 1 (HSF1) protein, the master regulator of HSP expression, is also a promising target for cancer therapy due to its involvement in tumorigenesis. This study is the first to investigate the potential of two novel curcumin analogs, MS13 (1,2-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one) and MS17 (1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one), as modulators of these key targets. Employing molecular docking and molecular dynamics (MD) simulations, we investigated the interactions of MS13 and MS17 with HSF1 and the panel of HSPs. Both compounds demonstrated strong binding affinity for all the proteins, particularly for HSP70, exhibiting greater affinity compared to curcumin. Molecular docking revealed specific binding sites for both compounds on each target protein, which were further investigated using MD simulations. MS17 generally formed more stable complexes with HSP27, HSP40, HSP60, and HSP70, suggesting it might be a more potent modulator of these specific proteins. In contrast, MS13 displayed greater stability when bound to HSF1 and HSP90. These different variations could be attributed to variations in the chemical structures of MS13 and MS17, leading to distinct interactions with each protein’s binding site. MS13 and MS17 exhibit more advantageous ADMET profiles compared to curcumin, particularly in their predicted Blood–Brain Barrier (BBB) permeability and MS17’s superior passive membrane permeability and absorption. These findings highlight the potential of both MS13 and MS17 as promising leads for developing HSP modulators for cancer treatment. Full article

Atherosclerosis is now recognized as a chronic inflammatory disease of the arterial wall, in which perivascular adipose tissue (PVAT) has evolved from a passive structural component to a key player in regulating vascular homeostasis and the pathophysiology of atherosclerosis, playing an active, not just structural, role. PVAT surrounds blood vessels and influences them metabolically, immunologically, and vascularly by secreting adipokines, cytokines, and other bioactive mediators. Under physiological conditions, PVAT has protective roles, as it produces adiponectin, nitric oxide (NO), and other vasodilatory factors that help maintain vascular tone and reduce inflammation. In particular, brown-like PVAT (rich in Uncoupling Protein-1 (UCP1) and mitochondria) offers significant vasoprotective effects. Under pathological conditions (obesity, dyslipidemia, insulin resistance), PVAT undergoes a phenotypic transition towards a pro-inflammatory profile by increasing leptin, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) secretion and decreasing adiponectin, contributing to endothelial dysfunction, vascular smooth muscle cell (VSMC) proliferation, local immune cell recruitment, extracellular matrix (ECM) remodeling, and fibrosis. PVAT plays a complex role in vascular health and disease, interacting with systemic metabolism through the secretion of bioactive molecules. Metabolic imbalances can promote PVAT inflammation. Epigenetic alterations and micro ribonucleic acid (miRNAs) can influence PVAT inflammation, and modern imaging methods for PVAT assessment, such as the fat attenuation index (FAI) and artificial intelligence-assisted radiomic profiling, may become predictive biomarkers of cardiac risk. Future directions aim to identify biomarkers and develop targeted therapies that modulate PVAT inflammation and dysfunction in the context of cardiovascular diseases. Full article

Meeting the International Maritime Organization’s (IMO) 2050 targets for reducing greenhouse gas (GHG) emissions requires cost-effective solutions that minimize wind resistance without compromising safety, particularly for medium-sized multipurpose vessels (MPVs), which have been underrepresented in prior research. This study numerically evaluates 20 bow-mounted NaviScreen configurations using a coupled high-fidelity computational fluid dynamics (CFD) and finite element analysis (FEA) approach. Key design variables—including contact angle (35–50°), lower-edge height (1.2–2.0 m), and horn position (3.2–5.3 m)—were systematically varied. The sloped Type-15 shield reduced aerodynamic resistance by 17.1% in headwinds and 24.5% at a 30° yaw, lowering total hull resistance by up to 8.9%. Nonlinear FEA under combined dead weight, wind loads, and Korean Register (KR) green-water pressure revealed local buckling risks, which were mitigated by adding carling stiffeners and increasing plate thickness from 6 mm to 8 mm. The reinforced design satisfied KR yield limits, ABS buckling factors (>1.0), and NORSOK displacement criteria (L/100), confirming structural robustness. This dual-framework approach demonstrates the viability of NaviScreens as passive aerodynamic devices that enhance fuel efficiency and reduce GHG emissions, aligning with global efforts to address climate change by targeting not only CO2 but also other harmful emissions (e.g., NOx, SOx) regulated under MARPOL. The study delivers a validated CFD-FEA workflow to optimize performance and safety, offering shipbuilders a scalable solution for MPVs and related vessel classes to meet IMO’s GHG reduction goals. Full article

The performance of passive target localization is significantly influenced by the positions of unmanned aerial vehicle swarms (UAVs). In this paper, we investigate the problem of UAV path optimization to enhance the localization accuracy. Firstly, a passive target localization signal model based on the time difference of arrival (TDOA) algorithm, which is then improved by the Chan method and Taylor series expansion, is established. Secondly, the Cramer–Rao lower bound (CRLB) of the modified TDOA algorithm is derived and adopted as the evaluation criterion to optimize the UAVs’ positions at each time step. Different from the existing works, in this paper, we consider the UAVs to have variable speed; therefore, the feasible region of the UAVs’ positions is changed from a circle into an annular region, which will extend the feasible region, enhancing the localization accuracy while increasing the computation complexity. Thirdly, to improve the efficiency of the UAV path optimization algorithm, the particle swarm optimization (PSO) algorithm is applied to search for the optimal positions of the UAVs for the next time step. Finally, numerical simulations are conducted to verify the validity and effectiveness of the proposals in this paper. Full article

Stabilization of the resonance frequency in thin-film acoustic devices to variations in environmental conditions is commonly reduced to the passive or active compensation of a single factor (usually temperature) and the isolation or addition of a separate correction circuit for every other factor (e.g., pressure and mass loading). In this work, the possibility of dual-factor compensation is proposed, where the response of a multi-layered thin structure to both temperature and ambient pressure variation vanishes due to the choice of intrinsic parameters (materials and thickness ratios). The response functions are derived for the $S_0$ Lamb mode at long wavelengths in an explicit analytical form in terms of bulk material characteristics. It is demonstrated that the dual-factor intrinsic stabilization requires at least a three-layered structure and can be achieved for materials commonly used in temperature-compensated devices (aluminum nitride, fused silica, and aluminum). Identification of the key material characteristics governing the existence of a stability solution can serve for a targeted search of such composites and implementation of new thin-film dual devices. Full article

Finite element (FE) modeling has emerged as a powerful computational approach in cardiovascular biomechanics, enabling detailed simulations of myocardial stress, strain, and hemodynamics, which are challenging to measure with conventional imaging techniques. This narrative review explores the progression of cardiac FE modeling from research-focused applications to its increasing integration into clinical practice. Specific attention is given to the mechanical effects of myocardial infarction, the limitations of conventional LV volume-reduction surgeries, and novel therapeutic approaches like passive myocardial reinforcement via hydrogel injections. Furthermore, the review highlights the critical role of patient-specific FE simulations in optimizing LV assist device parameters and guiding targeted device placements. Cutting-edge developments in artificial intelligence-enhanced FE modeling, including surrogate models and precomputed simulation databases, are examined for their potential to facilitate real-time, personalized therapeutic decision-making. Collectively, these advancements position FE modeling as an essential tool in precision medicine for structural heart disease. Full article