Search Results (149)

Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease are characterized by progressive neuronal loss, driven mainly by the misfolding, aggregation, and accumulation of each disease’s specific proteins. These pathogenic aggregates, including tau, α-synuclein, TDP-43, and huntingtin, disrupt cellular proteostasis and initiate cascades of neuroinflammation, oxidative stress, mitochondrial dysfunction, and synaptic failure. While protein aggregation has been a long-recognized hallmark of these disorders, growing evidence points towards a more complex interplay of initial molecular pathways with defects in RNA processing, stress granule pathology, and cell-type-specific vulnerability. Notably, such events may manifest differentially with respect to sex and are further modulated by age-related loss of the protein quality control processes like the ubiquitin–proteasome pathway, autophagy–lysosome pathway, and molecular chaperones. This review synthesizes current insights into the structural and functional dynamics of protein aggregation and its significance for neuronal well-being. It highlights the role of post-translational modifications, prion-like transmission, and aggregation kinetics in the regulation of toxicity. The review further discusses promising therapeutic strategies centered on restoring proteostasis, including small molecules that inhibit aggregation, protein clearance pathway enhancers, immunotherapy, antioxidant therapy, and diagnostic prospects such as the identification of reliable molecular signatures in bodily fluids that can reflect pathological changes even before clinical symptoms emerge. Advancements in single-cell transcriptomics and multi-omics platforms, which are changing our understanding of disease onset and progression and opening avenues for precision medicine and personalized treatments, were also discussed. Ultimately, deciphering the molecular logic that distinguishes physiological from pathological protein assemblies and understanding how cellular systems fail to adapt under stress will be key to the development of effective, disease-modifying therapies for these debilitating disorders. Full article

Although the role of OsHY5L2 in promoting photomorphogenic development is well characterized, its function in regulating rice quality is poorly understood. In this study, we found that OsHY5L2 plays an important role in regulating starch metabolism and modulating its fine structure and physicochemical properties. Overexpression of OsHY5L2 significantly reduced the chalky grain rate and degree of chalkiness but dramatically increased the head rice rate. OsHY5L2 was found to negatively regulate the accumulation of starch in rice endosperm by inhibiting starch biosynthesis and promoting starch hydrolysis. Transcriptomic analysis revealed that OsHY5L2 mainly regulated the expression of genes encoding enzymes involved in starch and sucrose metabolism. Moreover, OsHY5L2 overexpression induced the formation of numerous pinhole structures on the surfaces of starch granules. Analysis of the amylopectin chain length distribution showed that overexpression of OsHY5L2 decreased the proportion of ultra-short chains (DP 6–7) and intermediate chains (DP 13–24) of amylopectin while increasing the proportion of short chains (DP 8–12) and long chains (DP 25–36). Further studies demonstrate that OsHY5L2 overexpression altered the pasting properties of rice starch by affecting its multi-level structure and function. The results of this study improve our understanding of the functions of OsHY5L2 in regulating rice quality. Full article

The efficient resource utilization of industrial solid wastes, such as ground granulated blast-furnace slag (GGBS) and coal gangue (CG), is essential for sustainable development. However, their activation commonly depends on expensive and corrosive chemical alkalis. This study proposes a solution by developing a fully waste-based cementitious material using calcium carbide slag (CS), another industrial residue, as an eco-friendly alkaline activator for the GGBS-CG system. The influence of CS dosage (0–20 wt%) on hydration evolution and mechanical properties was examined using uniaxial compression testing, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The results indicated that a CS dosage of 10 wt% yielded the highest compressive strength, reaching 10.13 MPa—a 16.5% improvement compared to the 20 wt% group. This enhancement is ascribed to the formation of hydrotalcite (HT) and calcium silicate hydrate (C-(A)-S-H) gel, which densify the microstructure. In contrast, higher CS contents led to a passivation effect that restrained further reaction. This work offers a practical and theoretical basis for the development of low-carbon, multi-waste cementitious materials and presents a promising strategy for large-scale valorization of industrial solid wastes. Full article

Percocypris pingi was listed in the China Vertebrate Red List in 2015, and albino P. pingi exhibits remarkable ocular phenotypes due to melanin synthesis defects, including the deficiency of melanin granules in the iris and retinal pigment epithelium (RPE). However, the regulatory mechanism of pigment loss in the eyes of albino P. pingi has not yet been clarified. This study systematically revealed the potential mechanisms underlying the obstruction of ocular melanin synthesis in albino P. pingi through histopathological analysis, transcriptomics, and proteomics techniques. The results showed that the synergistic effects of abnormal H⁺ transport mediated by SLC45A2, excessive activation of retinol metabolism, and cytoskeletal transport disorders led to the inhibition of tyrosinase activity and retention of pigment granules, ultimately causing melanin deficiency in the eyes. This study first elucidates the molecular network of ocular albinism in fish from a multi-omics perspective, providing a new perspective for the mechanistic research of pigmentation disorders in vertebrates. Full article

Purpose: This case series examines the feasibility and outcomes of using a multi-tissue extracellular matrix (ECM) powder as an adjunct to standard wound care in a conflict zone. Primary objectives were granulation by day 7, wound closure, and minimizing early complications among patients with complex ballistic and blast injuries in Gaza during the 2024 Israeli military offensive. Methods: A retrospective observational study was conducted at the European Gaza Hospital from April to June 2024. Fifteen patients with high-energy soft tissue injuries who received ECM powder (XCellistem™) after surgical debridement were included. Data were extracted from operative reports, wound documentation, and clinical follow-up. Outcomes included granulation by day 7, wound closure method, and complications such as infection or dehiscence. Results: All 15 patients (median age 28; 14 male) sustained severe trauma, with 80% having exposed bone or tendon. ECM was applied directly to wound beds and often co-applied with vancomycin. Granulation tissue was observed in 12 patients by day 7, and 13 achieved wound closure via grafting, flap coverage, or secondary intention. No adverse reactions to ECM were reported. Conclusions: Multi-tissue ECM powder seems feasible and safe under austere conditions and appeared to support wound healing in severely injured patients. Its shelf stability, ease of use, and regenerative potential make it a promising adjunct for surgical care in resource-constrained conflict zones. Full article

Rough sets and fuzzy sets are two complementary approaches for modeling uncertainty and imprecision. Their integration enables a more comprehensive representation of complex, uncertain systems. However, existing rough fuzzy sets models lack the expressive power to fully capture the interactions among structural uncertainty, cognitive hesitation, and multi-level granular information. To address these limitations, we achieve the following: (1) We propose intuitionistic fuzzy covering rough membership and non-membership degrees based on maximal description and construct a new single-granulation model that more effectively captures both the structural relationships among elements and the semantics of fuzzy information. (2) We further extend the model to a multi-granulation framework by defining optimistic and pessimistic approximation operators and analyzing their properties. Additionally, we propose a neutral multi-granulation covering rough intuitionistic fuzzy sets based on aggregated membership and non-membership degrees. Compared with single-granulation models, the multi-granulation models integrate multiple levels of information, allowing for more fine-grained and robust representations of uncertainty. Finally, a case study on real estate investment was conducted to validate the effectiveness of the proposed models. The results show that our models can more precisely represent uncertainty and granularity in complex data, providing a flexible tool for knowledge representation in decision-making scenarios. Full article

The rapid advancement of artificial intelligence is transforming agriculture by enabling data-driven plant disease monitoring and decision support. Soil-borne mosaic wheat virus (SBWMV) is a soil-transmitted virus disease that poses a serious threat to wheat production across multiple ecological zones. Due to the regional variability in environmental conditions and symptom expressions, accurately evaluating the severity of wheat soil-borne mosaic (WSBM) infections remains a persistent challenge. To address this, the problem is formulated as large-scale group decision-making process (LSGDM), where each planting plot is treated as an independent virtual decision maker, providing its own severity assessments. This modeling approach reflects the spatial heterogeneity of the disease and enables a structured mechanism to reconcile divergent evaluations. First, for each site, field observation of infection symptoms are recorded and represented using intuitionistic fuzzy numbers (IFNs) to capture uncertainty in detection. Second, a Bayesian graph convolutional networks model (Bayesian-GCN) is used to construct a spatial trust propagation mechanism, inferring missing trust values and preserving regional dependencies. Third, an enhanced spectral clustering method is employed to group plots with similar symptoms and assessment behaviors. Fourth, a feedback mechanism is introduced to iteratively adjust plot-level evaluations based on a set of defined agricultural decision indicators sets using a multi-granulation rough set (ADISs-MGRS). Once consensus is reached, final rankings of candidate plots are generated from indicators, providing an interpretable and evidence-based foundation for targeted prevention strategies. By using the WSBM dataset collected in 2017–2018 from Walla Walla Valley, Oregon/Washington State border, the United States of America, and performing data augmentation for validation, along with comparative experiments and sensitivity analysis, this study demonstrates that the AI-driven LSGDM model integrating enhanced spectral clustering and ADISs-MGRS feedback mechanisms outperforms traditional models in terms of consensus efficiency and decision robustness. This provides valuable support for multi-party decision making in complex agricultural contexts. Full article

Background/Objectives: Combination therapies using traditional Chinese medicine and Western drugs have gained attention for their enhanced therapeutic effects and reduced side effects. Toujie Quwen Granules (TQG), known for its antiviral properties, particularly against respiratory viruses, could offer new treatment strategies when combined with antiviral drugs like arbidol, especially for diseases such as Coronavirus disease. This study investigates the synergistic mechanisms between arbidol and components from TQG against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M^pro). Methods: We identified compounds from TQG via existing data. Multi-ligand molecular docking, pharmacokinetic/toxicity screening, and preliminary simulations were performed to assess potential synergistic compounds with arbidol. UPLC-Q-Exactive Orbitrap-MS verified the presence of these compounds. Extended simulations and in vitro assays, including Luciferase and surface plasmon resonance, validated the findings. Results: Five compounds interacted with arbidol in synergy based on docking and preliminary dynamics simulation results. Only Baicalein (HQA004) could be identified in the herbal remedy by untargeted metabolomics, with ideal pharmacokinetic properties, and as a non-toxic compound. Extended simulations revealed that HQA004 enhanced arbidol’s antiviral activity via a “Far” Addition Mechanism #2, with an optimal 2:1 arbidol:HQA004 ratio. The movements of arbidol (diffusion and intramolecular conformational shifts) in the system were significantly reduced by HQA004, which may be the main reason for the synergism that occurred. In vitro experiments confirmed an increased inhibition of M^pro by the combination. Conclusions: HQA004 demonstrated synergistic potential with arbidol in inhibiting M^pro. The development of combination therapies integrating Western and herbal medicine is supported by these findings for effective antiviral treatments. Full article

The application of organic manure is a crucial agronomic practice for enhancing crop quality. This study aimed to elucidate the effects of organic manure and nitrogen fertilizers on the physicochemical properties of waxy maize starch. A field experiment was conducted with two cultivars (JKN768 and SYN2) and six fertilization treatments: no nitrogen fertilizer application (T1); constant nitrogen fertilizer application (T2); and the replacement of 20% (T3), 40% (T4), 60% (T5), and 100% (T6) of nitrogen fertilizer with organic manure. The combined application of organic manure and nitrogen fertilizer improved the morphology and volume-weighted mean diameter of starch granules and reduced the relative crystallinity and enthalpy gelatinization of the starch. Compared with T2, the treatment in which 40% of the nitrogen fertilizer was replaced with organic manure (T4) significantly increased the volume-weighted mean diameter of starch granules in JKN768 and decreased it in SYN2, while it increased the content of rapidly digestible starch in JKN768 and SYN2 by 7.85% and 4.96%, respectively. Additionally, T4 decreased the relative crystallinity of starch in JKN768 and SYN2 by 7.12% and 3.72%, respectively, while it decreased the content of slowly digestible starch in JKN768 and SYN2 by 20% and 13.45%, respectively. The results of this study highlight that replacing 40% of nitrogen fertilizer with organic manure can significantly enhance the multi-scale structural characteristics of waxy maize starch, and they provide theoretical support for the improvement of waxy maize starch quality. Full article

Stress granules (SG), dynamic cytoplasmic condensates formed via liquid-liquid phase separation (LLPS), serve as a critical hub for cellular stress adaptation and antiviral defense. By halting non-essential translation and sequestering viral RNA, SG restrict viral replication through multiple mechanisms, including PKR-eIF2α signaling, recruitment of antiviral proteins, and spatial isolation of viral components. However, viruses have evolved sophisticated strategies to subvert SG-mediated defenses, including proteolytic cleavage of SG nucleators, sequestration of core proteins into viral replication complexes, and modulation of stress-responsive pathways. This review highlights the dual roles of SG as both antiviral sentinels and targets of viral manipulation, emphasizing their interplay with innate immunity, autophagy, and apoptosis. Furthermore, viruses exploit SG heterogeneity and crosstalk with RNA granules like processing bodies (P-bodies, PB) to evade host defenses, while viral inclusion bodies (IBs) recruit SG components to create proviral microenvironments. Future research directions include elucidating spatiotemporal SG dynamics in vivo, dissecting compositional heterogeneity, and leveraging advanced technologies to unravel context-specific host-pathogen conflicts. This review about viruses and SG formation helps better understand the virus-host interaction and game process to develop new drug targets. Understanding these mechanisms not only advances virology but also informs innovative strategies to address immune escape mechanisms in viral infections. Full article

This study explores the effects of Tricholoma matsutake-derived insoluble dietary fiber (TMIDF) on the pasting behavior, structural properties, and in vitro digestibility of rice flour. The incorporation of 5% TMIDF significantly increased the peak viscosity (from 2573.21 to 2814.52 mPa·s) by competitively adsorbing water and forming a dense transient network, while simultaneously reducing the final viscosity (from 1998.27 to 1886.18 mPa·s) by inhibiting amylose recrystallization. Multi-scale structural analyses revealed that TMIDF enhanced V-type crystallinity and limited enzyme access via a porous fibrous matrix. Fourier-transform infrared spectroscopy and low-field nuclear magnetic resonance analyses confirmed that hydrogen bonding and water redistribution were key interaction mechanisms. TMIDF significantly lowered in vitro starch digestibility and increased resistant starch content by 16% (from 14.36% to 30.94%) through synergistic effects, including physical encapsulation of starch granules, formation of enzyme-resistant amylose-lipid complexes, and α-amylase inhibition (31.08%). These results demonstrate that TMIDF possesses a unique multi-tiered modulation mechanism, involving structural optimization, enzyme suppression, and diffusion control, which collectively surpasses the functional performance of conventional plant-derived insoluble dietary fibers. This research establishes a theoretical basis for applying fungal insoluble dietary fibers to develop low glycemic index functional foods, highlighting their dual role in improving processing performance and nutritional quality. Full article

Improving the manufacturability of drug formulations via direct compression has been of great interest for the pharmaceutical industry. Selecting excipients plays a vital role in obtaining a high-quality product without the wet granulation processing step. In particular, for diluents which are usually present in a larger amount in a formulation, choosing the correct one is of utmost importance in the production of tablets via any method. In this work, we assessed the possibility of manufacturing a small-molecule drug product, omeprazole, which has been historically manufactured via a multi-step processes such as wet granulation and multiple-unit pellet system (MUPS). For this purpose, four prototypes were developed using several diluents: a co-processed excipient (Microcelac^®), two granulated forms of alpha-lactose monohydrate (Tablettose^® 70 and Tabletose^® 100), and a preparation of microcrystalline cellulose (Avicel^® PH102) and lactose (DuraLac^® H), both of which are common excipients without any enhancement. The tablets were produced using a single punch tablet press and thoroughly characterized physically and chemically in order to assess their functionality and adherence to drug product specifications. The direct compression process was used for the manufacturing of all proposed formulations, and the prototype formulated using Microcelac^® showed the best results and performance during the compression process. In addition, it remained stable over twelve months under 25 °C/60% RH conditions. Full article

Ambrosia beetles (Coleoptera: Curculionidae: Scolytinae) in the tribe Xyleborini are economically important pests of woody ornamentals, tree nuts, and fruit orchards, including pecans in the United States. Among them, the granulate ambrosia beetle, Xylosandrus crassiusculus (Motschulsky), is the most common species in pecan orchards in Georgia. Various traps, including ethanol-mediated Lindgren multi-funnel traps, panel traps, bottle traps, sticky cards, and ethanol-infused wooden bolts, are used in ambrosia beetle monitoring programs. Trap color and placement height are important factors that increase trap effectiveness. To improve trap effectiveness for ambrosia beetles, we conducted a color and height preference experiment under field conditions using six different colored sticky cards, including black, blue, green, red, transparent, and yellow, placing them at three different heights (15, 60, and 120 cm from ground level). The results show that red and transparent sticky cards consistently captured a higher number of ambrosia beetles, whereas yellow-colored sticky cards consistently captured a lower number of ambrosia beetles compared to all other tested colors of sticky cards. A similar trend was observed with X. crassiusculus in field and laboratory settings. Among the evaluated trap heights, more ambrosia beetles, including X. crassiusculus, were consistently captured in the sticky cards placed at a height of 60 cm from the ground surface. Additionally, we monitored natural infestations of ambrosia beetles in commercial pecan orchards in Georgia and found more damage to pecan trees near the ground surface (45 cm) compared to the upper parts. We also recorded three ambrosia beetle species, X. crassiusculus, the black stem borer, X. germanus (Blandford), and the Southeast Asian ambrosia beetle, Xylosandrus amputatus (Blandford). Among them, X. crassiusculus (90.50%) was the most abundant species in the pecan orchards. Therefore, red and transparent sticky cards placed at a height of 45 to 60 cm could improve the trap efficacy and can be used for monitoring ambrosia beetles in pecan orchards. Full article

A ternary geopolymer mortar (TGM) was synthesized using steel slag (SS), granulated blast furnace slag (GGBS), and fly ash (FA) as raw materials. The effect of the SS content (0–60%) and the GGBS/FA mass ratio (5:1 to 1:5) on the TGM’s setting time was studied. To address the issue of rapid setting, the impact of different mixing methods ((A) dry mixing, (B) pre-dissolution, and (C) pre-coating) and dosages of BaCl₂ on the setting and hardening properties of TGM was further explored. The hydration product evolution and microstructural characteristics were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectrometry (EDS), with an in-depth analysis of the retarding mechanism of BaCl₂. The results indicate that, as the steel slag content increases, the setting time of TGM significantly shortens. The setting time decreases slightly with an increase in the GGBS/FA mass ratio. The mixing method influences the retarding effect of BaCl₂, with the C method showing significant advantages over both the A and B methods. Under the C mixing method, BaCl₂ consumes the alkaline components (SiO₃²⁻) in the alkaline activator and forms a BaSiO₃ coating layer on the precursor surface, which further delays the hydration process of the precursor particles. This study provides a promising approach for the high-value utilization of multi-source solid waste and suggests that future research should focus on large-scale application strategies and long-term performance evaluation to support its practical use in sustainable construction. Full article

Aim: In addition to numerous benefits provided by nanosuspensions (NSs) (e.g., enhanced saturation solubility, increased area for interaction with fluids), they suffer from major stability, handling and compliance issues. To overcome these challenges, we evaluated the feasibility of hot melt extrusion (HME) in transforming a cinnarizine-based NS, selected as a case study, into granules for oral intake. Methods: Thermoplastic polymers, in principle compatible with the thermal behavior of the selected drug and characterized by different interaction mechanisms with aqueous fluids, were used as carriers to absorb the NS and were processed by HME. Results: The extruded granules pointed out good physio-technological characteristics, a drug content > 85% with coefficient of variation (CV) < 5% and tunable in vitro performance coherent with the polymeric carriers they were composed of. Particle size as well as the solid state of cinnarizine was checked using several analytical techniques in combination (e.g., DSC, SEM, FT-IR, Raman). Depending on the composition of the granules, and specifically for formulations processed below 85 °C, the drug was found to remain crystalline and in the desired nanoscale. Conclusions: HME turned out to be a versatile process to transform, in a single-step, NSs into multi-particulate solid products for oral administration showing a variety of release profiles. Full article