Plants and animals respond to pathogens through pattern recognition receptor and Nod-like receptor proteins1. Pathogens commonly use protein effectors to suppress host immunity for successful infection2. However, the existence of non-protein effector classes remains comparatively understudied. Here we report an RNA-RNA recognition mechanism governing pathogen-host interaction, mediated by a regulatory RNA-encoding DNA sequence that separately generates two complementary regulatory RNAs. Specifically, a long non-coding RNA transcribed from this DNA region in the fungal pathogen Magnaporthe oryzae translocates into host rice cells and sequesters a complementary microRNA (miRNA), derived from a distinct host DNA region, thereby subverting host immunity. In turn, this rice-derived miRNA promotes disease resistance by repressing the expression of PKR1, a gene that encodes a negative regulator of host immunity. Sequestration of the host miRNA by the fungal long non-coding RNA releases PKR1 expression to facilitate fungal infection. We discovered that this regulatory RNA-encoding DNA sequence is probably widely present across diverse life species, mediating interactions between pathogens and their plant hosts. Collectively, our findings provide an approach for effective disease control using miRNAs derived from this important DNA region.

Next-generation food-preservation packaging is advancing rapidly, yet industrial translation remains limited because preservation claims are often disconnected from migration-derived exposure, toxicological thresholds, and the documentation required for regulatory approval under the intended conditions of use. This review reframes packaging innovation as an evidence-chain problem that must connect engineering design to measurable preservation performance, exposure control, and regulatory feasibility across major jurisdictions. We critically examine three dominant technology pathways: bio-based polymers, nano-enabled composites including enzyme-mimetic nanomaterials, and intelligent packaging systems. We emphasize how structural design choices govern barrier performance, controlled release, antimicrobial activity, and signal reliability. We synthesize migration and toxicology considerations, highlight the roles of non-intentionally added substances and degradation products in bio-based systems, and discuss the additional physicochemical characterization and release testing burden created by nanoscale additives. For intelligent packaging, we focus on calibration to food-specific spoilage kinetics and the practical advantages of noncontact label architectures that reduce migration risk while preserving interpretability. By integrating these dimensions, we propose a comparative prioritization logic that identifies configurations with the highest near-term readiness and defines the minimum evidence package needed for credible deployment. Overall, multilayer and compatibilized bio-based platforms currently offer the most direct route to scale. Nano-enabled functions require immobilization and robust proof of low migration to be feasible. Intelligent systems are most implementable in label-based noncontact formats supported by stability validation and decision thresholds linked to food quality endpoints. PRACTICAL APPLICATIONS: The proposed performance-safety-feasibility framework offers practical guidance for the design and evaluation of advanced food packaging systems. It can support the optimization of biodegradable and active materials, enhance intelligent freshness monitoring, and assist industry and regulatory bodies in material selection and safety assessment.

Accurate molecular property prediction is a cornerstone of modern chemical science, driving progress in drug discovery, materials design, and environmental research. Yet, most existing models remain unimodal, while multimodal approaches often rely on simple aggregation, leaving much of the complementary chemical information underexploited. In this work, we present a multimodal feature fusion framework that unites the strengths of deep chemical language processing (CLP) models and molecular fingerprints, integrating sequential and structural representations for more comprehensive molecular characterization. Unlike previous heuristic combinations, our framework systematically investigates the principles of effective cross-modal fusion. We benchmark ten CLP architectures and eight fingerprint types through exhaustive combinatorial search to identify the most synergistic configurations. This exploration shows that aggregating multiple models does not necessarily improve performance; instead, successful fusion requires data-aware design guided by feature integration and complementarity. The proposed strategy effectively couples sequential features learned from SMILES with structural information captured by molecular fingerprints, resulting in a coherent and chemically interpretable molecular representation. Evaluated across 60 datasets from MoleculeNet and TOXRIC, our fusion models deliver consistent and substantial gains over state-of-the-art baselines. Beyond outperforming existing architectures, this work provides conceptual insights and practical guidelines for multimodal fusion in molecular property prediction, highlighting the importance of efficient fusion strategies in building robust and generalizable molecular models. Scientific contribution This study provides a large-scale empirical evaluation of multimodal feature fusion for molecular property classification by systematically integrating SMILES-based chemical language representations with fingerprint-based structural descriptors across 60 benchmark datasets. The framework introduces a data-aware combinatorial fusion strategy to identify task-specific complementary feature combinations, improving robustness and interpretability compared with unimodal models and baseline approaches. The results clarify how sequence-based and structure-based molecular representations complement each other, providing practical guidance for designing multimodal models in cheminformatics.

Ferroptosis, an iron‑dependent and lipid peroxidation‑driven form of regulated cell death, has emerged as a key contributor to neuronal degeneration in protein misfolding disorders. However, how cellular energy metabolism modulates ferroptotic susceptibility in neurodegenerative proteinopathies remains incompletely defined. The present study investigated whether the previously described energy stress‑AMP-activated protein kinase (AMPK)‑acetyl‑CoA carboxylase (ACC) ferroptosis checkpoint operates in disease‑relevant neuronal proteinopathy models. Pharmacological and genetic interventions, cell viability assays, lipid peroxidation measurements, western blotting, RNA interference, and behavioral analyses were performed in SH‑SY5Y cells, transgenic Caenorhabditis elegans (C. elegans), and 3xTg‑AD mice. In SH‑SY5Y cells, glucose deprivation, 2‑deoxy‑D‑glucose (2DG), or 5‑aminoimidazole‑4‑carboxamide ribonucleoside reduced ferroptotic cell death induced by erastin or RSL3 and attenuated ferroptosis‑associated neuronal injury induced by amyloid precursor protein, α‑synuclein A53T, and polyQ74. This protection was associated with AMPK activation, ACC1 phosphorylation, reduced lipid peroxidation, sensitivity to ferroptosis inhibition, glutathione peroxidase 4 restoration, and acyl‑CoA synthetase long‑chain family member 4 suppression. AMPK inhibition or knockdown weakened the protection conferred by glucose deprivation, while aak‑2 RNAi attenuated the protective effects of 2DG in C. elegans, supporting a substantial contribution of AMPK‑ACC1‑associated signaling to ferroptosis suppression under energy stress. Consistently, 2DG or liproxstatin‑1 reduced ferroptosis‑associated oxidative damage and improved behavioral or cognitive deficits in transgenic C. elegans and 3xTg‑AD mice. These findings extend the established AMPK‑ACC ferroptosis checkpoint to neurodegenerative proteinopathy models and support energy stress‑associated AMPK‑ACC1 signaling as an important metabolic defense mechanism against ferroptosis‑related neuronal injury.

Ferroptosis contributes to aging-associated functional decline, yet compounds with robust organismal efficacy and defined upstream regulatory mechanisms remain limited. Here, we established a diethyl maleate (DEM)-induced glutathione depletion model in wild-type (N2) Caenorhabditis elegans as a survival-based screening platform and identified syringaresinol (Syr) as a leading hit from an in-house small-molecule library. In nematodes, Syr improved survival under DEM challenge, reduced lipid peroxidation, reactive oxygen species (ROS), and malondialdehyde levels, and alleviated age-associated oxidative lipid stress and iron imbalance during natural aging, accompanied by extended lifespan and improved healthspan-related phenotypes. In primary human foreskin fibroblasts, Syr conferred dose-dependent protection against RSL3- or erastin-induced ferroptosis, preserved cellular integrity, suppressed lipid peroxidation and ROS, and restored expression of GPX4, SLC7A11, and ferritin. In two senescence models, Syr also attenuated senescence-associated phenotypes and ferroptosis-related oxidative lipid stress, concomitant with recovery of GPX4 expression. Network-based prediction and functional perturbation identified HIF-1α as a candidate mediator of Syr-associated cytoprotection. HIF-1α knockdown weakened Syr-mediated protection and largely prevented GPX4 restoration, whereas GPX4 knockdown did not alter HIF-1α abundance. These findings support a functional HIF-1α-GPX4 defense axis in fibroblasts, while direct transcriptional regulation remains to be clarified. Overall, Syr attenuates ferroptosis-relevant oxidative lipid stress and aging-associated phenotypes in C. elegans and human fibroblast models, supporting further mechanistic and mammalian in vivo validation.

Radiation-induced thrombocytopenia (RIT) is a major dose-limiting toxicity of radiotherapy, for which effective pharmacological interventions remain limited. Rhei Radix et Rhizoma (RR) is widely used in traditional medicine, yet its thrombopoietic activity and molecular basis have not been systematically defined. Here, we investigated the effects of RR on thrombopoiesis using an integrated herbal-to-molecule and transcriptomic strategy. RR extract and representative phytochemicals were screened for megakaryocyte (MK) differentiation in Meg-01, K562, and murine haematopoietic stem and progenitor cells (HSPCs), followed by validation in a mouse RIT model. Network pharmacology and transcriptomic analyses indicated that RR regulates thrombopoiesis through coordinated multi-pathway modulation. Emodin was identified as the principal bioactive constituent mediating these effects. Functionally, emodin promoted MK maturation and polyploidization in vitro, accelerated megakaryopoiesis and platelet recovery in irradiated mice. Integrated target prediction and experimental validation identified ESR1 as a direct functional target of emodin, supported by molecular docking, molecular dynamics simulations, CETSA, and DARTS assays. Mechanistically, emodin activated ESR1-dependent PI3K/AKT and JAK2/STAT3 signaling, leading to induction of lineage-specific transcription factors and enhanced platelet biogenesis. Collectively, these findings identify emodin as a key thrombopoietic constituent of RR and reveal an ESR1-centered regulatory axis in megakaryopoiesis, supporting its therapeutic potential for RIT.

Alzheimeru2019s disease (AD), an aging-related disease, is characterized by chronic neuroinflammation and microglial activation, leading to neuronal death. Targeting the NOD-like receptors family pyrin domain containing 3 (NLRP3) inflammasome may offer therapeutic benefits. Through extensive screening of a natural herbal library using lipopolysaccharide/nigericin-stimulated BV-2 microglial cells, we discovered that Oenothera biennis, a plant-based functional food, significantly enhanced cell survival and inhibited the NLRP3 inflammasome. This was achieved by downregulating its component proteins and suppressing pyroptosis. Similar protective effects were observed in amyloid u03B2 (Au03B2) 1u201342-stimulated BV-2 cells, where O. biennis water extract (OWE) reduced inflammasome activity and modulated microglial phagocytic function. Additionally, OWE protected neuronal PC12 cells from inflammatory damage, underscoring its neuroprotective potential. Further mechanistic studies revealed that OWE activated autophagy by regulating the AMP-activated protein kinase-phosphoinositide 3-kinase/v-akt murine thymoma viral oncogene homolog/mammalian target of rapamycin (AMPK-PI3K/AKT/mTOR) signaling pathway. The effects of OWE on NLRP3 inflammasome inhibition and pyroptosis were reversed by treatment with bafilomycin A1 and compound C, indicating that autophagy plays a key role in these processes. In vivo studies showed that OWE activated autophagy and ameliorated Au03B2-induced paralysis and death in Caenorhabditis elegans. Furthermore, OWE demonstrated neuroprotective effects in 3xTg-AD mice by improving cognitive functions and reducing inflammatory markers through autophagy induction. Collectively, our findings suggest that OWE, as a plant-based functional food, inhibits the activation of the NLRP3 inflammasome in microglia via AMPK-PI3K/AKT/mTOR-mediated autophagy, providing a promising therapeutic avenue for AD.

Abstract Background Alzheimer’s disease (AD) is characterized by Tau aggregation, mitochondrial dysfunction, and oxidative stress, yet effective interventions targeting these pathological cascades remain limited. Therapeutic strategies that enhance autophagic and mitophagic clearance, attenuate Tau toxicity, and restore mitochondrial homeostasis are crucial for AD management. Methods This study investigated the neuroprotective effects of Pulsatilla chinensis extract (PCE) in SH-SY5Y neuronal cells and Caenorhabditis elegans (C. elegans) models of Tauopathy. Autophagic flux was evaluated by GFP-LC3 puncta formation, LC3-II conversion, and p62 degradation. Mitochondrial function was assessed through reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and ultrastructural analysis. The roles of autophagy and mitophagy were examined using 3-methyladenine (3-MA) and the Parkin inhibitor AC220. In C. elegans, locomotion, Tau aggregation, oxidative stress, and mitophagosome formation were assessed, and pink-1 knockdown was used to confirm mitophagy dependence. Results PCE significantly enhanced autophagic flux, decreased total and phosphorylated Tau (p-Tau Ser404) levels, and improved neuronal viability. It significantly reduced ROS accumulation, maintained MMP, and preserved mitochondrial morphology under both Tau overexpression and H2O2-induced oxidative stress. Inhibition of autophagy or Parkin-mediated mitophagy negated these protective effects. In C. elegans, PCE ameliorated neuromuscular dysfunction, suppressed Tau inclusions, and reduced oxidative injury, while the loss of pink-1 abolished its benefits, underscoring the critical role of mitophagy. Conclusion PCE exerts potent neuroprotective effects by promoting mitophagy, reducing Tau phosphorylation and aggregation, and restoring mitochondrial integrity. These findings reveal a novel mechanism linking mitochondrial quality control with Tau proteostasis and highlight PCE as a promising natural therapeutic candidate for AD. Graphical Abstract

Thrombocytopenia is a common hematological disorder characterized by reduced platelet counts and an increased risk of bleeding, for which current pharmacological treatments are often limited by adverse effects, drug resistance, or high costs. Traditional Chinese medicinal herbs such as ginseng, notoginseng, peony root, and astragalus have long been used for blood-nourishing and qi-tonifying purposes and are frequently prescribed for conditions associated with blood deficiency and hematopoietic dysfunction. This review systematically summarizes glycoside compounds derived from these herbs, focusing on their structural characteristics and pharmacological activities relevant to thrombocytopenia. Accumulating evidence indicates that glycosylation enhances the solubility, bioavailability, and stability of aglycones, thereby influencing their biological effects. Preclinical studies suggest that glycoside compounds may improve the hematopoietic microenvironment through anti-inflammatory, antioxidant, and immunomodulatory actions, potentially reducing immune-mediated platelet destruction. In addition, they may promote thrombopoiesis by modulating hematopoietic signaling pathways, such as PI3K/AKT, and by restoring immune balance, particularly via regulation of the Treg/Th17 axis. Collectively, these multi-target effects on hematopoiesis and immune regulation highlight glycoside compounds as promising lead candidates for the development of novel therapeutic approaches to thrombocytopenia.

Current therapeutic strategies for diabetic wounds struggle to simultaneously address the multifaceted pathological challenges, including oxidative stress, infection, inflammatory imbalance, and impaired angiogenesis. To overcome this limitation, we developed a multifunctional biomimetic nanoplatform named PLTm@CMCLP. In vitro experiments demonstrated its potent reactive oxygen species (ROS)-scavenging capacity, significant antibacterial activity, and excellent biocompatibility. Crucially, in a diabetic rat model with full-thickness skin defects, PLTm@CMCLP significantly accelerated wound healing by mitigating inflammatory responses and enhancing collagen deposition. Mechanistic investigation revealed that these therapeutic effects were mediated through the targeted regulation of the phosphodiesterase 4C/cyclic adenosine monophosphate/protein kinase A (PDE4C/cAMP/PKA) signaling pathway. Specifically, PLTm@CMCLP inhibited PDE4C expression, thereby restoring cAMP homeostasis and activating the downstream cAMP response element-binding protein (CREB) transcriptional program to promote tissue repair. Furthermore, plasmid transfection experiments confirmed that PDE4C overexpression attenuated the activation of this downstream pathway by PLTm@CMCLP. This study not only identifies the PDE4C/cAMP/PKA axis as a key regulator in diabetic wound healing but also provides a promising targeted therapeutic strategy for chronic wounds.

Ethnopharmacological relevance Sanguisorba officinalis L., a traditional Chinese hemostatic herb, is described in classical texts as having the dual function of “cooling and tonifying the blood.” Modern clinical studies have confirmed its significant efficacy against myelosuppression induced by cancer therapy, notably in elevating platelet counts in patients. However, the specific active components responsible for this effect and their underlying mechanisms remain unelucidated. Aim of the study Building on the traditional hemostatic efficacy of Sanguisorba officinalis L., this study elucidates the effects and mechanisms of its active monomer, epigallocatechin (EGC), in promoting megakaryocyte differentiation and platelet production for the treatment of thrombocytopenia. Materials and methods In this study we evaluated the ability of EGC to promote megakaryocyte differentiation of model cells in vitro. Its hematopoietic effects in vivo were further assessed using zebrafish and mouse models of RIT. To pinpoint the core targets of EGC against RIT, we utilized network pharmacology, complemented by experimental validation with molecular biology techniques to elucidate its pro-hematopoietic mechanisms mediated through the estrogen receptor. Results EGC effectively enhanced megakaryocyte differentiation and platelet production in vitro and in vivo, without detectable toxicity. Integrated network pharmacology and molecular validation revealed ERα-mediated signaling as the primary mechanism underlying EGC’s activity. Mechanistically, EGC promoted megakaryocyte differentiation by activating ERα-mediated SRC/PI3K/AKT signaling and modulating hematopoietic transcription factors. Conclusions EGC promotes megakaryocyte differentiation via ERα-mediated activation of the SRC/PI3K/AKT pathway and subsequent regulation of hematopoietic transcription factors for the treatment of thrombocytopenia.

Cellular senescence, a stress-induced state of stable cell cycle arrest accompanied by a senescence-associated secretory phenotype (SASP), plays a paradoxical role in cancer biology. On the one hand, senescent cells function as a barrier to tumor initiation by activating the DNA damage response (DDR) and tumor suppressor pathways such as p53/p21 and p16INK4a-retinoblastoma (RB). On the other hand, their long-term persistence promotes chronic inflammation, immune evasion, and tissue remodeling via sustained SASP, ultimately facilitating tumor progression, metastasis, and therapeutic resistance. This review elucidates the hallmarks of cellular senescence, explores its dual roles and mechanistic underpinnings in tumor suppression and promotion, highlighting the key molecular circuits governing the senescence phenotype, such as telomere dynamics, autophagy-lysosome function, and immunosurveillance. We further examine targeted therapeutic approaches, such as senolytics and senomorphics, and their integration into sequential induction and clearance regimens. These interventions aim to leverage the transient SASP to enhance immune recognition while minimizing the pro-tumorigenic effects associated with persistent SASP. Despite these advances, challenges such as tissue specificity, off-target effects, biomarker inconsistency, and cellular heterogeneity remain major hurdles to clinical translation. To transcend the traditional static and binary perspective of senescence, we introduce a dynamic plasticity model that conceptualizes senescence as a context-dependent and dynamically regulated program, potentially reversible and modulated by molecular switches, temporal patterns of SASP, and microenvironmental factors. Targeting these plasticity checkpoints holds promise for optimizing "one-two punch" combination regimens and expanding immunotherapeutic windows, thereby offering a novel paradigm for improving outcomes in aging-related cancers.

ETHNOPHARMACOLOGICAL RELEVANCE:Chuanminshen violaceum Sheh et Shan is a medicinal-and-edible Apiaceae plant in China recorded for yin nourishment, lung/spleen tonification, and phlegm resolution, and used for cough and chronic respiratory complaints. STUDY AIM:To synthesize current evidence on botanical resources, chemistry, pharmacology, and applications of C. violaceum, and to define priorities for standardized and safe development. MATERIALS AND METHODS:This review integrates studies on resource distribution and ecological adaptability, multi-fraction phytochemistry, extraction-purification and formulation technologies, preclinical pharmacology, and quality, safety, and regulatory considerations. RESULTS:C. violaceum contains structurally diverse polysaccharides plus volatile oils (often polyacetylene-rich), phenolics (e.g., chlorogenic acid and rutin), PUFA-rich lipids, and newly reported minor constituents. Polysaccharides show variable monosaccharide profiles, molecular-weight ranges, and linkage/branching patterns, strongly influenced by extraction-purification; derivatization (e.g., sulfation/selenization) and delivery systems can further tune physicochemical properties. Preclinical studies report antioxidant, anti-inflammatory, immunomodulatory, cardioprotective, and antiviral effects, commonly linked to Nrf2/Keap1 redox defense, inflammatory signaling control, TLR2/4-related immune regulation, gut-barrier reinforcement with microbiota remodeling, and anti-ferroptotic protection in myocardial ischemia-reperfusion models. Applications span traditional dosage forms and functional foods, but translation is limited by origin/process variability, incomplete long-term safety and ADME data, and regulatory uncertainty. CONCLUSIONS:C. violaceum is a promising ethnomedicinal resource with clear part-specific features and polysaccharide-centered potential. Future work should combine multi-omics with target validation, fingerprint-guided QC and traceability, greener scalable processing, and regulatory-aligned safety packages to enable reproducible products.

The development of integrated technologies capable of simultaneously detecting and degrading pollutants symbolizes a transformational breakthrough in next-generation water treatment strategy, and overcomes the limitations of traditional single-function systems for monitoring and remediation. This study proposes an innovative sodium percarbonate (SPC)/alpha-MnO2/light strategy to establish a dual-functional platform capable of both photoelectrochemical (PEC) detection and advanced oxidation process (AOP) degradation, aiming to achieve precise detection and efficient removal of doxorubicin (DOX). The system strategically adjusts light sources (ultraviolet for detection, visible light for degradation), not only achieves high-sensitivity real-time detection (limit of detection: 0.40 ng center dot mL- 1, 10x lower than conventional methods) but also significantly improves degradation efficiency (37 %-38 % improvement over unitary components), resolving crucial limitation of traditional single-function technologies. The portable PEC platform integrates an alpha-MnO2-modified electrode, SPC-enhanced system, a portable electrochemical workstation and smartphone-based analytical software, which enables rapid on-site quantitative analysis of DOX. Meanwhile, SPC/alpha-MnO2/light system can synergistically generate multiple reactive oxygen species (ROS) including center dot OH, center dot O2- , 1O2 and center dot CO3- , achieve nearly complete mineralization of DOX and generate low-toxicity or even non-toxic byproducts. Mechanistic study reveals that oxygen vacancies and Mn2+/Mn3+/Mn4+ redox cycle in alpha-MnO2 (alpha-MN) jointly serve as core reaction centers, and synergistically interacts with H2O2/CO32- derived from SPC, not only driving efficient separation of photogenerated charge carriers in alpha-MN but also promoting the sustained generation of reactive free radicals. Notably, the system demonstrates excellent salt tolerance and broad pH adaptability in various actual water sources (tap, pond, and river water). Further, achieving 100 % removal of DOX (30 mg center dot L- 1) within 30 min under natural sunlight validates its practicality for solar-driven degradation. This work pioneers a "One-for-Two" strategy, which establishing a novel "detect-to-treat" environmental governance paradigm that provides a sustainable, scalable solution for addressing water pollution.

Herbal self-assembled nanoplatforms (H-SANs) represent an emerging strategy in herbal nanomedicine by integrating the intrinsic bioactivity of phytochemicals with supramolecular nanoscale organization. Unlike conventional nanocarriers that may be limited by low drug loading, excipient burden, premature release, and scale-up complexity, H-SANs are carrier-free or predominantly bioactive systems formed through noncovalent interactions, including π-π stacking, hydrogen bonding, hydrophobic forces, electrostatic interactions, and metal coordination, among polyphenols, flavonoids, alkaloids, terpenoids, saponins, and related phytochemical components. Reported assemblies can achieve high drug loading, exhibit stimuli-responsive structural changes under disease-associated cues such as acidic pH, redox imbalance, or enzyme overexpression, and can be further engineered with targeting motifs. Preclinical studies have explored their applications in oncology, inflammation, neurodegeneration, metabolic disorders, cardiovascular disease, antimicrobial therapy, wound repair, kidney injury, and bone disorders, where H-SANs may act as bioactive scaffolds as well as delivery systems. However, their translational development remains constrained by dilution-dependent instability, incomplete understanding of in vivo disassembly and parent-drug regeneration, protein corona formation, tumor transport heterogeneity, raw-material variability, manufacturing reproducibility, regulatory classification, and limited human-relevant pharmacokinetic and safety evidence. Emerging strategies, including AI-assisted modeling, rational multicomponent co-assembly, continuous manufacturing, and improved biological validation, may help address these challenges. Overall, H-SANs provide a promising but still largely preclinical framework for high-payload herbal nanomedicine, and their clinical value will require rigorous physicochemical characterization, reproducible manufacturing, and cautious translational validation.

Novel carbon dots (CDs-1) were synthesized using Sanguisorba officinalis L., as a precursor and a deep eutectic solvent (DES) as both solvent and dopant. For comparison, CDs-2 were prepared under identical conditions but using water as solvent. Chemical analyses reveal that two CDs possess well-defined crystalline structures and are rich in diverse functional groups. Notably, DES-mediated synthesis endows CDs-1 with advantageous features compared to CDs-2, including higher N and Cl contents, enhanced hydrophilicity, and superior optical properties. To evaluate their potential biomedical applications, antioxidant capacities of them were investigated through in vitro and in vivo assays. Results demonstrated that both CDs exhibit potent free radical scavenging activity, strong KMnO4 reduction capability, and notable anti-cellular oxidative damage effects. Importantly, CDs-1 show superior performance in enhancing oxidative stress resistance at nematode level. Furthermore, owing to the exceptional optical characteristics, CDs-1 hold great promise for bioimaging applications and sensitive detection of 2,4,6-trinitrophenol (TNP).

Cuproptosis is a distinct form of regulated cell death triggered by copper and characterized by the aggregation of lipoylated mitochondrial proteins, destabilization of iron-sulfur cluster proteins, and proteotoxic stress. Unlike nonspecific copper toxicity, cuproptosis depends on a defined biochemical context shaped by FDX1-associated protein lipoylation, oxidative carbon metabolism, and mitochondrial substrate competence. These features may create a therapeutic vulnerability in tumors with high oxidative phosphorylation, but they also impose substantial translational challenges. Free copper ions and conventional copper ionophores often lack the tumor selectivity, pharmacological control, and safety required for systemic use, and copper exposure alone is insufficient unless it can be converted into sustained mitochondrial stress in susceptible tumor cells. Nanomedicine can provide spatiotemporal and chemical control over tumor copper stress. By enabling tumor-selective accumulation, stimulus-responsive activation, mitochondrial targeting, and modulation of copper homeostasis, nanoplatforms may help convert cuproptosis from a biochemical phenomenon into a therapeutically tractable strategy. These capabilities create opportunities to integrate cuproptosis with broader tumor vulnerabilities, including redox imbalance, metabolic plasticity, and altered immune states. This Review examines the molecular basis of cuproptosis and tumor susceptibility, the design and combination strategies of cuproptosis-oriented nanomedicines, and the translational challenges that must be addressed to move the field beyond proof of concept. Future advances are likely to depend on precise control of copper bioavailability and mitochondrial targeting, together with biomarker-guided patient selection and clinically tractable platform design.

Alzheimer's disease(AD),an aging-related disease,is characterized by chronic neuroinflammation and microglial activation,leading to neuronal death.Targeting the NOD-like receptors family pyrin domain containing 3(NLRP3)inflammasome may offer therapeutic benefits.Through extensive screening of a natural herbal library using lipopolysaccharide/nigericin-stimulated BV-2 microglial cells,we discovered that Oenothera biennis,a plant-based functional food,significantly enhanced cell survival and inhibited the NLRP3 inflammasome.This was achieved by downregulating its component proteins and suppressing pyroptosis.Similar protective effects were observed in amyloid β(Aβ)1-42-stimulated BV-2 cells,where O.biennis water extract(OWE)reduced inflammasome activity and modulated microglial phagocytic function.Additionally,OWE protected neuronal PC 12 cells from inflammatory damage,underscoring its neuroprotective potential.Further mechanistic studies revealed that OWE activated autophagy by regulating the AMP-activated protein kinase-phosphoinositide 3-kinase/v-akt murine thymoma viral oncogene homolog/mammalian target of rapamycin(AMPK-PI3K/AKT/mTOR)signaling pathway.The effects of OWE on NLRP3 inflammasome inhibition and pyroptosis were reversed by treatment with bafilomycin A1 and compound C,indicating that autophagy plays a key role in these processes.In vivo studies showed that OWE activated autophagy and ameliorated Aβ-induced paralysis and death in Caenorhabditis elegans.Furthermore,OWE demonstrated neuroprotective effects in 3xTg-AD mice by improving cognitive functions and reducing inflammatory markers through autophagy induction.Collectively,our findings suggest that OWE,as a plant-based functional food,inhibits the activation of the NLRP3 inflammasome in microglia via AMPK-PI3K/AKT/mTOR-mediated autophagy,providing a promising therapeutic avenue for AD.

Developing safe and sustainable antimicrobial strategies is critical for postharvest fruit preservation. In this work, corn silk, an abundant agri-food byproduct with a long history of food and medicinal use, was upcycled into fluorescent carbon dots (CS-CDs) via a green hydrothermal route (yield: 27.3%). The resulting CS-CDs were quasi-spherical (∼1.8 nm) and enriched with oxygen-/nitrogen-containing surface groups, exhibiting excitation-dependent blue-green photoluminescence (λ_em ≈ 492 nm at λ_ex = 414 nm). CS-CDs displayed broad-spectrum antibacterial activity against Pseudomonas fluorescens and Staphylococcus aureus, with higher potency against the Gram-negative strain. Mechanistic assays supported a multimodal bactericidal action involving rapid membrane permeabilization (live/dead staining, NPN uptake, and SEM evidence), cytoplasmic leakage, elevated intracellular ROS, and suppressed metabolic activity. CS-CDs also inhibited the postharvest fungal pathogen Penicillium expansum in vitro and reduced decay severity on plums and citrus fruits, as reflected by dose-dependent decreases in lesion area (mm2). When applied as a surface coating (≤1.0 mg/mL), CS-CDs extended the shelf life of jujubes and strawberries by mitigating weight loss and browning, and by lowering microbial loads (CFU/fruit) during storage. Importantly, a practical safety window was supported at functional concentrations, with low cytotoxicity in mammalian cells and no detectable adverse effects on the growth, locomotion, or reproduction of Caenorhabditis elegans. Overall, corn-silk-derived carbon dots provide a promising green antimicrobial platform for postharvest fruit preservation and offer a scalable strategy for valorizing agricultural residues.

This study introduces a highly crystalline yellow fluorescent covalent organic framework, COF-W, and its electrospun nanofiber membrane, COF-W-PP, for the simultaneous detection and adsorption of amphotericin B (AMB). COF-W was synthesized through Schiff-base condensation between 3,6-diaminocarbazole (DAC) and 2,5dimethoxyterephthalaldehyde (DMTP), forming a D-it-A structure that exhibits fluorescence via intramolecular charge transfer (ICT). Its porous framework and imine bonds enable specific AMB capture through hydrogen bonding and it-it interactions, which disrupts the ICT balance and results in fluorescence quenching and color changes, which is establishing a dual-mode fluorescence/colorimetric detection platform. The electrospun COFW-PP membrane, fabricated by incorporating COF-W into a PVP/PVDF polymer matrix on the non-fluorescence filter paper, enhances material stability and usability. COF-W demonstrates high selectivity for AMB, with a detection limit (LOD) of 0.02 & micro;M and a maximum adsorption capacity of 379.98 mg & sdot;g- 1. In real water and plasma samples, detection recoveries range from 79.38% to 114.39%, and adsorption efficiency exceeds 91%. COF-W-PP membrane shows a clear colorimetric response: color gradation intensifies with increasing AMB concentration, enabling rapid on-site detection when paired with smartphone analysis software. Mechanism studies indicate that recognition and quenching are synergistically driven by multiple hydrogen bonds, static quenching, photoinduced electron transfer (PET), and inner filter effect (IFE). Furthermore, COF-W displays good biocompatibility and low cytotoxicity, supporting its potential use in biological samples and in vivo analysis.