Search Results (4,421)

Background: Dahuang Xiaoshi Tang (DXT), an ancient Chinese herbal remedy dating back to 220 AD, as documented initially in “Treatise on Febrile and Miscellaneous Diseases,” is used to treat damp-heat jaundice with interior sthenia syndrome. In DXT, anthraquinones and alkaloids form insoluble complexes, reducing its effectiveness. A revised herbal extract, DXT-M, was developed, and its hepatoprotective properties were demonstrated in animal models using pharmacodynamic, metabolomic, network pharmacological, and toxicological approaches. Methods: The α-naphthalene isothiocyanate was utilised to establish the acute liver injury rat model. The assays of glutamate pyruvate transaminase, glutamic oxalacetic transaminase, alkaline phosphatase, bilirubin, total bile acid, complement 3 (C3) and C4, interleukin-2 (IL-2) and IL-6, tumour necrosis factor α (TNF-α), and pathological morphology were used to evaluate the hepatoprotection of DXT in comparison to DXT-M. The ¹H-NMR-based serum and urine metabolomics were performed to identify potential biomarkers and metabolic pathways of DXT-M in treating hepatitis. The intrinsic regulatory mechanisms of DXT in liver protection, as well as the combination of network toxicology, were elucidated. Statistical analyses included RM two-way ANOVA with Geisser–Greenhouse correction and Dunnett’s post hoc test for longitudinal data, and one-way ANOVA with Dunnett’s post hoc test for group comparisons. Data were shown as mean ± SD. Results: Liver-injured animals exhibited weight loss, ruffled fur, and liver damage, accompanied by elevated liver function indicators. DXT-M effectively improved these symptoms, repaired liver damage, restored liver function, and regulated immune status by modulating complement 3. Metabonomics and other analyses indicated the CYP/GST-ROS axis is key to its hepatoprotective effects. DXT-M outperformed DXT in efficacy. Conclusions: DXT-M demonstrated significant effectiveness in restoring liver pathological damage, correcting abnormal biochemical indicators of liver function, and regulating complement factors. The pathway of CYP/GST-ROS served as the shared regulatory axis and transformation site for DXT-M’s liver protective effects. These findings suggest that DXT-M has potential as a treatment for acute liver injury, highlighting the need for further research into its underlying molecular mechanisms as well as its complete material basis. This study’s main limitation is its focus on acute models; future research should include other liver diseases and clinical observation to evaluate its full potential. Full article

Hypopharyngeal carcinoma (HPC) represents the most prognostically unfavorable subtype among head and neck malignancies. Platinum-based neoadjuvant chemotherapy serves as a critical therapeutic approach for improving outcomes in hypopharyngeal carcinoma; however, its efficacy remains suboptimal due to the high incidence of chemoresistance. Current research on chemoresistance has primarily focused on head and neck squamous cell carcinoma (HNSCC), yet significant heterogeneity exists between hypopharyngeal carcinoma and other head and neck tumors, limiting the direct applicability of broader HNSCC research findings to hypopharyngeal carcinoma. This review systematically summarizes recent advances in understanding the mechanisms underlying chemoresistance in hypopharyngeal carcinoma, with emphasis on the comprehensive elucidation of key mechanisms, including apoptosis evasion, enhanced DNA damage repair, augmented autophagy, and increased drug efflux. Moreover, three noteworthy special scenarios involving cancer stem cells (CSCs), epithelial–mesenchymal transition (EMT), and cancer-associated fibroblasts (CAFs) are discussed. These entities not only intrinsically participate in multiple chemoresistance mechanisms but also interact synergistically, thereby further exacerbating chemoresistance in hypopharyngeal carcinoma. Full article

The structure, chemical composition, thermal stability, and abuse responses of cathode materials are critical to the safety and economy of lithium-ion batteries (LIBs). This review systematically summarizes advances in research on how cathode materials influence LIB thermal runaway (TR) behavior. It analyzes the oxygen release from cathodes in TR mechanisms and the hazards of such oxygen generation during TR, expounds on how differences in cathode structure, chemical composition, and thermal stability affect TR behavior, and summarizes the thermal characteristics of LIBs with different cathodes under mechanical, electrical, and thermal abuse. Results indicate that oxygen released from cathode decomposition during TR oxidizes electrolytes, releasing substantial heat and gas and causing more severe TR hazards. Structural instability of cathodes leads to accelerated release of lattice oxygen, speeding up TR initiation. Chemical composition regulates thermal stability, phase transition pathways, and gas generation rates during TR, while elemental ratios affect the ease of TR triggering. Cathodes with poor thermal stability have lower thermal decomposition onset temperatures, making TR more likely to occur and intensifying reaction severity. All three abuse types trigger inherent risks of cathodes, inducing TR and significantly increasing its occurrence probability. Differences in intrinsic properties further extend to the system level, also influencing thermal runaway propagation and fire dynamics at the module level. Future research focusing on the intrinsic properties of cathodes and external abuse is of great significance for addressing LIB TR behavior. Full article

To ensure the highest safety standards in modern automobiles, the industry is constantly adopting zero-defect frameworks, such as AEC-Q100, which aims for defective-parts-per-billion (DPPB) or grade-0 level reliability standards in automotive integrated-circuit (IC) packages. Most contemporary wire-bonded packages use either pure copper (Cu) or palladium (Pd)-coated copper (PCC) wires bonded to aluminum (Al) bond pads as interconnections. This choice is made due to their lower cost and superior electrical and mechanical performance, compared to traditional gold wire-based devices. However, these Cu–Al wire-bonded interconnections are prone to ion-induced lift-off/open-circuit corrosion failures when exposed to even trace amounts (<20 ppm) of extrinsic and/or intrinsic halide (Cl⁻ and Br⁻) contaminants, decreasing device longevity. This study investigates corrosion failure mechanisms in Cu and PCC wire-based devices by subjecting non-encapsulated devices to a highly accelerated aqueous-immersion screening test containing 100 ppm chloride (Cl⁻), 100 ppm bromide (Br⁻), and a mixed-ion solution (MX: Cl⁻ + Br⁻). The screening results indicate that even control PCC-Al devices with a Pd overlayer can be susceptible to Cl⁻ and Br⁻ induced corrosion, with 21 ± 1.6% lift-off failures in MX-solution. In contrast, applying a novel Cu-selective passivation reduced lift-off to 3.3 ± 0.6% and introducing phosphonic-acid-based inhibitor into the MX solution eliminated lift-off failures, demonstrating markedly improved reliability. Full article

The significant negative thermal expansion (NTE) that occurs in La(Fe,Si)₁₃-based alloys during magnetic transition make them promising to combine with positive thermal expansion (PTE) materials to obtain near-zero thermal expansion (NZTE) materials. However, La(Fe,Si)₁₃-based alloys with NTE generally show intrinsic poor mechanical properties. Here, thermal expansion properties are optimized by adding Ag in La_0.6Ce_0.4(Fe_0.91Co_0.09)_11.9Si_1.1 to form a multi-phase structure exhibiting enhanced compressive strength. Through spark plasma sintering (SPS) and annealing, the samples consisted of α-Fe(Co,Si), NaZn₁₃-type, and LaAg₂ phases. When the annealing temperature reaches 1323 K, LaAg₂ disappears and is replaced by La₂O₃. The LaAg₂ phase and α-Fe(Co,Si) phase contribute as PTE materials to compensate for the NTE of the NaZn₁₃-type phase. Near-zero thermal expansion was achieved in the temperature range of 240–294 K, with a coefficient of thermal expansion (CTE) of 3.5 ppm/K at a 9.581 at.% Ag content. Benefiting from the uniform phase distribution and coordinated deformation, the samples obtained high mechanical strengths, with fracture stresses of 1481.1 MPa for the 15 wt.% Ag sample. This work provides a promising route for high-strength and near-zero thermal expansion Ag/La(Fe,Si)₁₃ composites. Full article

Corbicula fluminea protein (CFP) and cyanidin-3-O-glucoside (C3G) are natural nutrient fortifiers. During consumption or processing, they may interact with each other, inducing alternations in their structural and functional properties. However, nothing was known about the mechanism of their interaction and their synergistic antioxidant effect. In this research, C3G was physically mixed with CFP to simulate practical scenarios. The impact of the presence of C3G on the multispectral characteristics, antioxidant activity, and particle properties of CFP was examined and compared to chemically fabricated C3G-CFP covalent conjugates. The results indicate that C3G tended to spontaneously bind to CFP and formed compact non-covalent complex, with hydrophobic forces predominantly governing the interaction. This binding resulted in the statically quenched intrinsic fluorescence of CFP, accompanied by a dynamic model. Moreover, C3G preferentially induced Trp residue in CFP exposed to a more polar microenvironment, yet it exerted nearly no effects on CFP when analyzed using ultraviolet–visible (UV-Vis) spectroscopy and synchronous fluorescence spectroscopy (SFS). Additionally, although the formed non-covalent complex demonstrated strengthened antioxidant capacity, C3G displayed an antagonistic effect with CFP, whereas lower C3G concentrations led to synergistic effects in covalent conjugates. These findings provide new insights into the effective application of C3G and CFP as nutritional antioxidants. Full article

Dermatan sulfate (DS) is an animal glycosaminoglycan with significant structural heterogeneity and a high, but variable density of negative electric charge. Owing to these characteristics DS displays a high degree of biological reactivity that is subject to regulation. We previously demonstrated that structural variants of DS rapidly induce moderate necroptosis in luminal breast cancer cells. In the present study, we investigated the intracellular molecular mechanism(s) that may underlie this effect, focusing on the expression of key regulators of intrinsic (BCL-2A1) and extrinsic (cFLIP) apoptosis, autophagy (Beclin-1), and oxidative stress protection (heme oxygenase-1 (HO-1)). Using RT-qPCR, Western blotting, immunofluorescence, and pharmacological inhibition, we have shown for the first time that DS, depending on its structure and the cancer cell line, can rapidly, albeit transiently, upregulate either the long or short cFLIP splicing variant and also reduce the level of HO-1. These effects are mediated via DS-triggered PI3K and/or NFκB signaling. Moreover, DS can also influence the intracellular distribution of these proteins. In contrast, this glycan did not affect the expression of BCL-2A1 and BECN1. These findings indicate that DS induces coordinated molecular remodeling in luminal breast cancer cells that creates an intracellular environment favorable for necroptosis induction. Full article

The escalating global threat of antimicrobial resistance (AMR) necessitates innovative therapeutic strategies beyond traditional antibiotic development. Drug repurposing offers a rapid, cost-effective approach by identifying new antibacterial applications for existing non-antibiotic drugs with established safety profiles. Emerging evidence indicates that diverse classes of non-antibiotic drugs, including non-steroidal anti-inflammatory drugs (NSAIDs), statins, antipsychotics, calcium channel blockers and antidepressants, exhibit intrinsic antibacterial activity, or potentiate antibiotic efficacy. This review critically explores the mechanisms by which drugs that are not recognised as antibiotics exert antibacterial effects, including efflux pump inhibition, membrane disruption, biofilm inhibition, and quorum sensing interference. We discuss specific examples that demonstrate reductions in minimum inhibitory concentrations (MICs) of antibiotics when combined with these drugs, underscoring their potential as antibiotic adjuvants. Furthermore, we examine pharmacokinetic considerations, toxicity challenges, and clinical feasibility for repurposing these agents as standalone antibacterials or in combination therapies. Finally, we highlight future directions, including the integration of artificial intelligence and machine learning to prioritise drug candidates for repurposing, and the development of targeted delivery systems to enhance bacterial selectivity while minimising host toxicity. By exploring the overlooked potential of non-antibiotic drugs, this review seeks to stimulate translational research aimed at leveraging these agents in combating resistant bacterial infections. Nonetheless, it is crucial to acknowledge that such drugs may also pose unintended risks, including gut microbiota disruption and facilitation of resistance development. Hence, future research should pursue these opportunities with equal emphasis on efficacy, safety, and resistance mitigation. Full article

Community detection is a crucial technique for uncovering latent network structures, analyzing group behaviors, and understanding information dissemination pathways. Existing methods predominantly rely on static graph structural features, while neglecting the intrinsic dynamic patterns of information diffusion and nonlinear attenuation within static networks. To address these limitations, we propose DAMA, a community detection model that integrates dynamic propagation-aware feature modeling with adaptive multi-hop structural aggregation. First, an Information Flow Matrix (IFM) is constructed to quantify the nonlinear attenuation of information propagation between nodes, thereby enriching static structural representations with nonlinear propagation dynamics. Second, we propose an Adaptive Sparse Sampling Module that adaptively retains influential neighbors by applying multi-level propagation thresholds, improving structural denoising and preserving essential diffusion pathways. Finally, we design a Hierarchical Multi-Hop Aggregation Framework, which employs a dual-gating mechanism to adaptively integrate neighborhood representations across multiple hops. This approach enables more expressive structural embeddings by progressively combining local and extended topological information. Experimental results demonstrate that DAMA achieves better performance in community detection tasks across multiple real-world networks and LFR-generated synthetic networks. Full article

Background/Objectives:Hydrogels are highly hydrated, biocompatible polymer networks increasingly investigated as drug-delivery systems (DDS) for analgesics. Their ability to modulate local release, prolong drug residence time, and reduce systemic toxicity positions them as promising platforms in perioperative, chronic, and localized pain settings. This scoping review aimed to systematically map clinical applications, efficacy, and safety of hydrogel-based DDS for analgesics, while also documenting non-DDS uses where the matrix itself contributes to pain modulation through physical mechanisms. Methods: Following PRISMA-ScR guidance, PubMed, Embase, and Cochrane databases were searched without publication date restrictions. Only peer-reviewed clinical studies were included; preclinical studies and non-journal literature were excluded. Screening and selection were performed in duplicate. Data extracted included drug class, hydrogel technology, clinical setting, outcomes, and safety. Protocol was registered with Open Science Framework. Results: A total of 26 clinical studies evaluating hydrogel formulations as DDS for analgesics were included. Most were randomized controlled trials, spanning 1996–2024. Local anesthetics were the most frequent drug class, followed by opioids, corticosteroids, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), and neuromodulators. Application sites were predominantly topical/transdermal and perioperative/incisional. Across the DDS cohort, most of the studies reported improved analgesic outcomes, including reduced pain scores and lower rescue medication use; neutral or unclear results were rare. Safety reporting was limited, but tolerability was generally favorable. Additionally, 38 non-DDS studies demonstrated pain reduction through hydrogel-mediated cooling, lubrication, or barrier effects, particularly in burns, ocular surface disorders, and discogenic pain. Conclusions: Hydrogel-based DDS for analgesics show consistent clinical signals of benefit across diverse contexts, aligning with their mechanistic rationale. While current evidence supports their role as effective, well-tolerated platforms, translational gaps remain, particularly for hybrid nanotechnology systems and standardized safety reporting. Non-DDS applications confirm the intrinsic analgesic potential of hydrogel matrices, underscoring their relevance in multimodal pain management strategies. Full article

Autoimmune gastritis (AIG) is a chronic, organ-specific autoimmune disease characterized by progressive destruction of gastric parietal cells driven by autoreactive CD4⁺ T-cells, epithelial stress pathways, and microbial factors. Parietal cell loss results in achlorhydria, intrinsic factor deficiency, and vitamin B12 malabsorption, ultimately leading to pernicious anemia. Compensatory hypergastrinemia promotes enterochromaffin-like (ECL) cell hyperplasia and contributes to the development of type 1 gastric neuroendocrine neoplasms (gNENs). These clinical consequences are well recognized, yet the cellular and molecular mechanisms driving mucosal atrophy and neoplastic transformation remain incompletely defined. Recent advances highlight the role of endoplasmic reticulum stress, impaired autophagy, innate immune effectors, and dysbiosis in perpetuating inflammation and epithelial injury. The frequent coexistence of AIG with other autoimmune disorders further adds to its clinical complexity. Therapeutic options remain limited, spanning vitamin B12 replacement and endoscopic management to emerging targeted approaches. Netazepide, a gastrin/CCK2 receptor antagonist, is the only agent tested in clinical trials, whereas interventions targeting ER stress, autophagy, immune tolerance, or microbiome composition are still in the preclinical stage. Clarifying these mechanisms is crucial to improve biomarker development, optimize surveillance, and identify targeted therapies to prevent neoplastic transformation. Full article

As an emerging innovation paradigm in the digital economy era, digital innovation has become an important means for manufacturing firms to build supply chain resilience for sustainable development, but its intrinsic mechanism requires clarification. This research explores the impact of digital innovation (digital organizational innovation and digital product innovation) on supply chain resilience (supply chain readiness, supply chain responsiveness, and supply chain recovery) and sustainable performance via structural equation modeling involving data from 226 Chinese manufacturing firms. The results show that digital organizational innovation can promote digital product innovation. Digital organizational innovation and digital product innovation contribute to supply chain readiness, supply chain responsiveness, and supply chain recovery. Supply chain readiness, supply chain responsiveness, and supply chain recovery enhance sustainable performance. Finally, supply chain resilience mediates the relationship between digital innovation and sustainable performance. These findings reveal the role of digital innovation in improving sustainable performance through supply chain resilience and provide practical guidance for manufacturing companies to better conduct digital innovation to build supply chain resilience and thus realize sustainable development. Full article

Galectins, a family of glycan-binding proteins, play crucial roles in various cellular functions, acting at both intracellular and extracellular levels. Among them, Galectin-3 (Gal-3) stands out as a unique member, possessing an intrinsically unstructured N-terminal oligomerization domain and a canonical carbohydrate-recognition domain (CRD). Gal-3 binding to glycosylated plasma membrane cargo leads to its oligomerization and membrane bending, ultimately resulting in the formation of endocytic invaginations. An interactomic assay using proteomic analysis of endogenous Gal-3 immunoprecipitates identified the orphan G protein-coupled receptor GPRC5A as a novel binding partner of Gal-3. GPRC5A, also known as Retinoic Acid-Induced protein 3 (RAI3), is transcriptionally induced by retinoic acid. Our results further demonstrate that extracellular recombinant Gal-3 stimulates GPRC5A internalization. In SW480 colorectal cancer cells, glycosylated GPRC5A interacts with Gal-3. Interestingly, while GPRC5A expression was upregulated by the addition of all-trans retinoic acid (ATRA), its endogenous internalization in SW480 cells was specifically triggered by extracellular Gal-3, but not by ATRA. This study provides new insights into the endocytic mechanisms of GPRC5A, for which no specific ligand has been identified to date. Further research may uncover additional Gal-3-mediated functions in GPRC5A cellular signaling and contribute to the development of innovative therapeutic strategies. Full article

The persistent conflict between strength and electrical conductivity in copper-based materials presents a fundamental limitation for next-generation high-performance applications. Graphene, with its unique two-dimensional architecture and exceptional intrinsic characteristics, has become a promising reinforcement phase for copper matrices. This comprehensive review synthesizes recent advancements in graphene–copper composites (CGCs), focusing particularly on structural design innovations and scalable manufacturing approaches such as powder metallurgy, molecular-level mixing, electrochemical deposition, and chemical vapor deposition. The analysis examines pathways for optimizing key properties—including mechanical strength, thermal conduction, and electrical performance—while investigating the fundamental reinforcement mechanisms and charge/heat transport phenomena. Special consideration is given to how graphene morphology, concentration, structural quality, interfacial chemistry, and processing conditions collectively determine composite behavior. Significant emphasis is placed on interface engineering strategies, graphene alignment, consolidation control, and defect management to minimize electron and phonon scattering while improving stress transfer efficiency. The review concludes by proposing research directions to resolve the strength–conductivity paradox and broaden practical implementation domains, thereby offering both methodological frameworks and theoretical foundations to support the industrial adoption of high-performance CGCs. Full article

Cognition is often modeled in terms of abstract reasoning and neural computation, yet a growing body of theoretical and experimental work suggests that the roots of cognition lie in fundamental embodied regulatory processes. This article presents a theory of cognition grounded in sensing, feeling, and affect—capacities that precede neural systems and are observable in even the simplest living organisms. Based on the info-computational framework, this entry outlines how cognition and proto-subjectivity co-emerge in biological systems. Embodied appraisal—the system’s ability to evaluate internal and external conditions in terms of valence (positive/negative; good/bad)—and the capacity to regulate accordingly are described as mutually constitutive processes observable at the cellular level. This concept reframes cognition not as abstract symbolic reasoning but as value-sensitive, embodied information dynamics resulting from self-regulating engagement with the environment that spans scales from unicellular organisms to complex animals. In this context, information is physically instantiated, and computation is the dynamic, self-modifying process by which organisms regulate and organize themselves. Cognition thus emerges from the dynamic coupling of sensing, internal evaluation, and adaptive morphological (material shape-based) activity. Grounded in findings from developmental biology, bioelectric signaling, morphological computation, and basal cognition, this account situates intelligence as an affect-driven regulatory capacity intrinsic to biological life. While focused on biological systems, this framework also offers conceptual insights for developing more adaptive and embodied forms of artificial intelligence. Future experiments with minimal living systems or synthetic agents may help operationalize and test the proposed mechanisms of proto-subjectivity and affect regulation. Full article