To meet the increasing demand for green and sustainable delivery systems in food, cosmetics, and pharmaceuticals and address the research gap in natural polyphenol-cellulose nanocrystal (CNC) composite stabilizers, this study developed a bio-based Pickering emulsion stabilizer via hydrogen bonding between 6’-O-caffeoylarbutin (CA) and CNCs. Results demonstrated CA/CNCs self-assembled into a dense interfacial layer, endowing the emulsion with exceptional stability that was reflected in over 85% curcumin enscapsulation efficiency after 30 days of dark storage and structural integrity at up to 80 °C, while CA-curcumin synergism enhanced antioxidant activity with 76.9% DPPH and 81.2% ABTS+ free radical scavenging rates. FT-IR, 1H NMR, and computational simulations confirmed the hydrogen-bond network between CA and cellobiose as the core stabilization mechanism. This study provides a novel, eco-friendly strategy for high-performance natural stabilizers, offering the advancement of green, functional delivery systems across relevant industries.

MRSA-infected wounds remain difficult to treat because of persistent bacterial colonization, biofilm formation, inflammation, and delayed tissue regeneration. Here, we developed a sustainable multifunctional wound dressing by incorporating Dendrobium crepidatum-derived carbon quantum dots (DCQDs) into a carboxymethyl chitosan–carboxymethyl cellulose (CMCS–CMC) hydrogel. The DCQDs exhibited nanoscale morphology, oxygen−/nitrogen-rich surface chemistry, partial graphitic structure, green fluorescence, and good aqueous dispersibility. Their incorporation into the CMCS–CMC matrix generated a mechanically reinforced hydrogel with improved local viscoelastic properties and ROS-generating ability. The DCQDs showed antibacterial activity against MRSA through a multi-target mechanism involving ROS-associated oxidative stress, suppression of SOD/catalase defenses, membrane depolarization, increased membrane permeability, and bacterial structural damage. Beyond planktonic killing, DCQDs reduced early bacterial adhesion, EPS and eDNA production, biofilm biomass, slime formation, and major virulence factors, indicating strong antibiofilm and antivirulence effects at sub-MIC levels. The CMCS–CMC–DCQDs hydrogel also showed sustained DCQD release, favorable cytocompatibility, and hemocompatibility. In MRSA-infected wound models, the hydrogel accelerated wound closure, reduced bacterial burden, improved collagen deposition and angiogenesis, and modulated inflammatory responses. Histological and immunohistochemical analyses revealed well-organized collagen deposition, angiogenesis, fibroblast activation, and M2 macrophage polarization. Overall, this work presents a plant-derived sustainable multifunctional hydrogel dressing that integrates antibacterial, antibiofilm, ROS-associated, anti-inflammatory, and tissue-regenerative functions for MRSA-infected wound management.

Measurable residual disease (MRD) has become a cornerstone of modern acute myeloid leukemia (AML) management, fundamentally transforming disease monitoring, prognostic stratification, and therapeutic decision-making. Although conventional morphologic assessment remains the standard for evaluating remission, it lacks the sensitivity required to detect low levels of persistent leukemia that frequently precede clinical relapse. Over the past decade, remarkable advances in immunophenotypic, molecular, and genomic technologies have substantially improved the accuracy and clinical utility of MRD assessment. Multiparameter flow cytometry and quantitative real-time polymerase chain reaction continue to represent the most widely implemented approaches in routine practice, while digital droplet polymerase chain reaction and error-corrected next-generation sequencing provide enhanced analytical sensitivity for molecular monitoring. More recently, single-cell sequencing, multi-omics technologies, liquid biopsy, and artificial intelligence–based analytical platforms have emerged as promising strategies for characterizing clonal evolution, leukemia stem cell persistence, treatment resistance, and individualized relapse risk. These innovations are driving the transition from static disease assessment toward dynamic precision monitoring throughout the entire treatment course, including induction therapy, consolidation, allogeneic hematopoietic stem cell transplantation, and post-transplant surveillance. Nevertheless, important challenges remain, including assay standardization, optimal MRD thresholds, discrimination between residual leukemia and clonal hematopoiesis, interlaboratory reproducibility, cost, and integration of multiple diagnostic platforms into routine clinical workflows. This review provides a comprehensive overview of the biological basis of MRD, critically examines current and emerging detection technologies, summarizes their clinical applications and limitations, and discusses future directions for MRD-guided precision medicine in AML. The continued integration of highly sensitive molecular diagnostics, single-cell and multi-omics profiling, liquid biopsy, and artificial intelligence is expected to redefine risk-adapted therapeutic strategies and further improve long-term outcomes for patients with AML.

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease with a rising global incidence rate, which poses a significant challenge to clinical management due to the limited efficacy and adverse reactions of current treatments. To overcome these limitations, we engineered Hes-Zn@IN, a novel core-shell nanoparticle system combining a hesperetin‑zinc (HesZn) metal-polyphenol coordination core encapsulated in an inulin (IN) polysaccharide shell. This nanotherapeutic platform exhibits synergistic therapeutic benefits: superior antioxidant capacity through metal-polyphenol coordination, demonstrating a 38% reduction in ROS and a 47% decrease in NO production in LPS-activated macrophages; robust immunomodulatory effects, significantly lowering pro-inflammatory cytokines (46% reduction in TNF-α, 42% in IL-6) while increasing anti-inflammatory IL-10 by 78%; a pH-dependent release profile enabling 1.85 times greater drug accumulation in inflamed colon tissue. In murine DSS-induced colitis models, oral administration of Hes-Zn@IN produced remarkable therapeutic outcomes, including 19.2% improvement in colon length, restoration of ZO-1 tight junction protein expression, and substantial mitigation of histopathological inflammation. Our findings establish this inulin-armored metal-polyphenol hybrid as a breakthrough nanomedicine that synergistically targets colonic redox-immune remodeling and barrier repair, presenting a comprehensive therapeutic approach for UC management.

Living cells are increasingly explored as drug carriers for their active targeting capacity, yet robust intracellular loading in vitro often fails to translate into efficacy in vivo. Here, we address this disconnect by loading macrophages with nano- and microdrugs with equal intracellular mass and matched release kinetics. Quantitative tracking revealed that in vitro retention overestimates in vivo stability: Nanodrug-loaded macrophages lost up to 83% of their payload after reinfusion, nearly double the loss observed in vitro. Nanodrug loading also elevated oxidative stress in macrophages, thereby impairing chemotactic migration. By contrast, microdrugs persisted intracellularly for ≥7 days and preserved macrophage migration toward inflamed sites. Using intravital imaging, we provided previously unavailable spatiotemporal evidence of vascular transmigration while retaining cargo. These properties translated into superior efficacy in systemic and localized inflammation models. Our findings underscore that effective cell-based drug delivery requires looking beyond uptake to evaluate in vivo cargo persistence and its impact on cell migration.

Microgels are attractive carriers for local drug delivery, but the poor compatibility of hydrophobic drugs with hydrophilic networks limits drug loading and causes uncontrolled release. Here, we present a microfluidicassisted confined antisolvent precipitation strategy that enables broadly applicable and efficient encapsulation of poorly soluble drugs inside microgels. Rapid solvent exchange inside microfluidic droplets triggers in situ supersaturation and crystallization of hydrophobic drugs before microgel gelation, creating a drug crystalline retention effect that stabilizes drug domains across gelling hydrophilic polymer networks. This mechanism not only enhances drug loading but also mitigates burst release. Importantly, the strategy is applicable to diverse hydrophilic polymer systems capable of rapid gelation, as shown by successful encapsulation of multiple hydrophobic drugs in both natural and synthetic microgels. Compared with conventional methods, the resulting drug-loaded microgels achieved over fivefold higher loading while maintaining a favorable morphology. To further strengthen drug-matrix interactions, tryptophan-grafted chitosan was developed, extending curcumin release for over three days. In a mouse gouty arthritis model, curcumin-loaded microgels enabled rapid suppression of anti-inflammatory cytokines, sustained immunomodulation, and functional joint recovery. Overall, this work establishes a broadly applicable platform for fabricating high-loading, long-acting microgels for the treatment of inflammatory and degenerative diseases.

Effective intra-articular therapy requires injectable depots that persist in the synovial space and modulate local inflammatory and oxidative microenvironments. Here, we developed a high-aspect-ratio short-fiber platform based on acid-labile acetalated dextran (AcDEX) for sustained intra-articular drug delivery. Continuous AcDEX fibermats electrospun from low-molecular-weight (10 kDa) dextran self-disintegrated within seconds into injectable short fibers (average aspect ratio ∼ 30) upon mild agitation in aqueous media, enabling on-demand preparation without post-processing. Resveratrol (RES), a hydrophobic antioxidant and anti-inflammatory compound, was encapsulated into AcDEX by blend electrospinning. RES@AcDEX fibers remained chemically intact during disintegration and provided sustained, pH-accelerated RES release (pH 6.8 vs 7.4) together with prolonged intra-articular retention, as evidenced by joint-confined fluorescence detectable for up to 10 days after injection. Released RES scavenged reactive oxygen species (ROS) in a dose-dependent manner, reduced intracellular ROS in lipopolysaccharide (LPS)-stimulated macrophages, and modulated inflammatory macrophage phenotypes in vitro. In a gouty arthritis model, a single intra-articular injection of RES@AcDEX short fibers reduced swelling, improved gait performance, downregulated proinflammatory cytokines, and upregulated anti-inflammatory cytokines in periarticular tissues. Overall, self-disintegrating AcDEX short fibers offer a simple and tunable, shape-engineered intra-articular depot for local modulation of ROS and inflammation, with potential utility for gouty arthritis and other inflammatory joint disorders.

Density functional theory (DFT) calculations were performed to elucidate the reaction mechanism of the Pd-catalyzed carbonylation of propargylic alcohol (1), leading to the efficient synthesis of cyclohexyl $α$-methylene-$β$-lactone (2). Our study revealed that the reaction proceeds through a four-step pathway: alkyne migration and insertion, CO insertion, HCl-assisted hydrogen transfer, and final C–O annulation. Notably, the final C–O annulation step was identified as the rate-determining step (RDS) of the overall catalysis, with a free energy barrier of 25.7 kcal/mol (i.e., $\mathbf{IM4}→\mathbf{TS4}).$ Additionally, we uncovered the critical role of the HCl during the reaction pathway, a demonstrating that it acts as a co-catalyst, proton shuttle, and hydrogen bond donor/acceptor. NBO, EDA-NOCV, and HIGM analyses further revealed that the remarkable stability of the transition state $\mathbf{TS3}$ in the presence of HCl primarily arises from strong electrostatic attraction and orbital interaction energies between the two interacting fragments. These mechanistic insights provide valuable insight and guidance for the rational design of new Pd-catalyzed transformations.

Cellulose nanocrystal (CNC)-based circularly polarized luminescent (CPL) materials, which are responsive to external stimuli, have attracted increasing attention in developing smart chiral photonic materials. In this study, chiral nematic bio-composite CNC films with right-handed (R-) CPL emission and tunable dissymmetry factors (glum) were prepared by encapsulating curcumin in chiral nematic CNC films via an evaporation-induced self- assembly strategy. The CPL active bio-composite CNC films exhibit multiple responsiveness to relative humidity (RH) and pH. It is noted that the pH response of the composite films is visualized, which is reflected in the variation of film colors, fluorescence, and CPL emission wavelengths. Additionally, with a hydrophobic treatment, the bio-composite CNC films exhibit enhanced water resistance and pH-responsive CPL in acid/base aqueous solutions. Based on the responsive circular polarization information, the bio-composite CNC films were developed as optical labels for multiple anti-counterfeiting applications. The reported environmentally friendly bio-composite CNC films provide a new reference for utilizing natural polysaccharides to build multi-mode responsive CPL materials.

Supramolecular hydrogels derived from low-molecular-weight gelators (LMWGs) have attracted considerable interest in drug delivery due to their exceptional biocompatibility and responsiveness to physiological microenvironments. However, fabricating microgel formulations based on LMWGs is extremely challenging due to the intrinsic fragility of the self-assembled networks. To mitigate the thermodynamic limitation of LMWGs, we developed an in-droplet self-assembly strategy to fabricate spherical supramolecular microgels. In this approach, mild droplet solidification ensures that ascorbyl palmitate (AP) molecules self-assemble into nanosheets through hydrophobic interactions and hydrogen bonding. As the droplets shrink, these nanosheets concentrate, interpenetrate with each other and form stable microgels. The palmitate-based prodrugs were successfully incorporated into the interdigitated bilayer structure, achieving high drug-loading degree (36.4-47.2 wt%). In vitro and in vivo studies confirmed the inflammation-responsive disassembly of these microgels, leading to flare-dependent, on-demand drug release. While both formulations exhibited comparable therapeutic efficacy in a standard inflammatory arthritis (IA) model, the disease-severity adaptive microgels demonstrated markedly superior therapeutic benefits in a severe IA model compared to non-responsive microspheres designed to resemble clinically utilized formulations. Overall, our results suggest inflammation-responsive supramolecular microgels enabled by controlled in-droplet self-assembly represent a promising next-generation platform for localized drug delivery, with strong potential for clinical translation.

Dynamic responsive structural colored materials have drawn increased consideration in a wide range of applications, such as colorimetric sensors and high-safety tags. However, the sophisticated interactions among the individual responsive parts restrict the advanced design of multimodal responsive photonic materials. Inspired by stimuli-responsive color change in chameleon skin, a simple and effective photo-crosslinking strategy is proposed to construct hydroxypropyl cellulose (HPC) based hydrogels with multiple responsive structured colors. By controlling UV exposure time, the structural color of HPC hydrogels can be effectively controlled in a full-color spectrum. At the same time, HPC hydrogels showcase temperature and mechanical dual-responsive structural colors. In particular, the microstructure of HPC hydrogels undergoes a transition from the chiral nematic phase to the nematic phase under the action of external stretching, leading to a significant reflection of circularly polarized light (CPL) to linearly polarized light (LPL). Given the diverse responsiveness exhibited by HPC hydrogels and their unique structural transition properties under external forces, we have explored their potential applications as dynamic anti-counterfeiting labels and optical skins. This work reveals the great possibility of using structural colored cellulose hydrogels in multi-sensing and optical displays, opening up a new path for the exploration of next-generation flexible photonic devices.

BACKGROUND:This study explored whether the cell cycle regulator cadherin 1 (CDH1) impacts colorectal cancer cell cycle and stemness via mediating ubiquitination of sirtuin 5 (SIRT5). METHODS:We first constructed CDH1 overexpression plasmid and small interfering RNA against SIRT5 (siSIRT5) and transfected them into HCT116/HT29 cells, followed by transfection efficiency verification. The effect of CDH1 on Cyclin F/SIRT5/CDH1 protein levels in HCT116/HT29 cells was verified by Western blot. After up-regulation of CDH1, changes in SIRT5 ubiquitination (immunoprecipitation), cell cycle (cell cycle kit), proliferation (5-Bromodeoxyuridine assay), and stemness marker expressions (qRT-PCR) in HCT116/HT29 cells were detected. Rescue assays were performed to examine cell proliferation and stemness marker expressions. RESULTS:Overexpression of CDH1 decreased Cyclin F expression and increased SIRT5 and CDH1 expressions in HCT116/HT29 cells. Up-regulation of CDH1 suppressed SIRT5 ubiquitination, promoted G0/G1 phase blockage in HCT116/HT29 cells, boosted cell proliferation into quiescence and enhanced cell stemness. siSIRT5 counteracted the regulatory effect of CDH1 overexpression on colorectal cancer cells. CONCLUSION:CDH1 promotes the entry of colorectal cancer cells into quiescence and enhances stemness by dampening SIRT5 ubiquitination.

To extend the photo-response range and quantum efficiency of titanium dioxide (TiO2), it was sensitized with lignin-derived red-emitting carbon dots (RCDs). The RCDs consisted of a base lignin structure and many types of functional groups (e.g., C-O, -NH2, -OSO3H, -NR2, and -OH). The optimal emission wavelength of the RCDs was 628 nm, with a fluorescence lifetime of 8.56 ns. The TiO2 photocatalyst particles were sensitized by RCDs, which narrowed the band gap of TiO2 and increased the efficiency of carrier photogeneration. The RCDs/TiO2 possessed a double band-gap structure with the band-gap energies of 1.60 and 3.13 eV. The photocurrent response of RCDs/TiO2 under simulated solar irradiation were 1.2 to 4.5 mu A center dot cm-2. The sensitization of TiO2 by RCDs facilitated the photocatalytic degradation of tetracycline. Under simulated sunlight, the degradation of tetracycline by RCDs/TiO2 reached 95.0 % and the mineralization ratio was 57.5 % within 60 min.

Cancer treatment remains challenging due to the complexity of the tumor microenvironment, which promotes tumor heterogeneity and contributes to the development of multidrug resistance, ultimately hindering drug delivery and reducing therapeutic efficacy. In recent years, biomimetic nanocarriers have emerged as promising tools to address these challenges. Among them, cancer cell membrane (CCM)-coated nanoparticles (CCM-NPs) have attracted increasing attention due to their unique advantages, including homologous targeting, prolonged circulation mediated by self-recognition, and enhanced tumor penetration. Moreover, CCM-NPs can serve as versatile platforms for tumor vaccines by leveraging their inherent tumor-associated antigens and immunomodulatory potential. By leveraging CCMs to functionalize NPs, researchers have developed innovative approaches to improve drug delivery, enhance tumor immunotherapy, and optimize cancer vaccine efficacy. Despite these advancements, a comprehensive review summarizing the latest progress in CCM-based biomimetic nanocarriers for tumor treatment is lacking. This review integrates recent advances in CCM-NPs for targeted drug delivery and cancer vaccination, and discusses their fabrication, characterization, mechanisms and applications across multiple cancer types, which provides timely insights to guide their future development in precision tumor therapy.

Liposomes are considered ideal drug carriers due to their excellent biocompatibility, non-immunogenic nature, and the ease of surface functionalization, making them widely applicable in clinical treatments for diseases, including cancer. Although liposomes possess inherent passive targeting capabilities, the ability to enhance drug accumulation in target tissues remains limited. Enhancing the active targeting of liposomes is, therefore, essential for improving drug delivery efficiency. Glycosylation modification of the liposomal surface has shown promise in improving targeting to specific cells or tissues. For example, incorporating sugars such as mannose or galactose on the liposomal surface can strengthen their interaction with cancer cells. Furthermore, glycosylated liposomes can be integrated with various therapeutic strategies, such as co-delivery of drugs and siRNA or the incorporation of specific peptides and antibodies, to enhance therapeutic effects. This review highlights recent advances in the development of active-targeting liposome drug carriers based on specific cell surface binding and examines the application of various glycosylated liposomes in targeted drug delivery. As an emerging drug delivery platform, glycosylated liposomes address the limitations of traditional liposomes and offer significant potential for the development of future nanomedicines. Future research will focus on elucidating the effects of glycosylation modification on liposomal performance to optimize their clinical applications and explore the potential for large-scale industrial production.

Traumatic brain injury (TBI) is a leading cause of chronic neurological deficits, with few effective therapies available. Although neural stem cells (NSCs) show promise for neural regeneration, they face limited survival and differentiation in the pathological TBI microenvironment. To address this issue, we developed a synergistic approach combining hydrogel encapsulation with ultrasound (US) stimulation to improve the viability and targeted differentiation of NSCs. We synthesized a biocompatible Schiff base hydrogel by conjugating carboxymethyl chitosan and phenylaldehyde polyethylene glycol phenylaldehyde. This hydrogel was then used to encapsulate NSCs derived from C57BL/6J mice. In vitro, US stimulation was found to significantly promote the differentiation of hydrogel-encapsulated NSCs into neural lineages and increase neurotrophic factor secretion. In vivo, the NSCs + hydrogel + US treatment exhibited improved behavioral performance, facilitated neural tissue regeneration, and increased growth factors expression in mice with TBI. These results suggest that the combination of hydrogel and US synergistically improves the survival rate of transplanted NSCs and promotes better neurological recovery by mitigating the negative effects of the microenvironment associated with TBI. This combination treatment strategy is a promising approach to enhancing the efficacy of NSCs-based interventions for TBI.

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy worldwide. Platinum(II)-based drugs, a cornerstone in CRC treatment, are often limited by significant side effects and suboptimal efficacy. Herein, we present a platinum(IV) prodrug nanoplatform (Pt(IV)-Cro NPs) designed to overcome these challenges through intracellular morphological transformation, enhancing therapeutic outcomes against CRC. Pt(IV)-Cro NPs are formed via the self-assembly of Pt(IV)-crocetin (Pt(IV)-Cro) and mPEG-crocetin (mPEG-Cro), driven by hydrophilic-hydrophobic interactions. These nanoparticles exhibit concentration-dependent morphology, transitioning from rod-shaped structures at lower concentrations to spherical forms at higher concentrations. Notably, Pt(IV)-Cro NPs undergo time-dependent morphological changes within cells. Upon uptake by CT26 cells, the nanoparticles retain a nanorod shape during the first hour but transform into spherical structures within 3 h. These morphological transitions contribute to a remarkable 141-fold reduction in the half-inhibitory concentration (IC50) against CT26 cells compared to cisplatin alone. Pt(IV)-Cro NPs induced 3.14-fold greater apoptosis, 51.2% mitochondrial depolarization, and 55.9% ROS elevation compared to cisplatin. In vivo studies in CT26 tumor-bearing mice reveal that Pt(IV)-Cro NPs significantly outperform cisplatin alone, reducing tumor growth by up to 8.08 times relative to controls. This innovative nanoplatform combines enhanced efficacy with minimized side effects, offering a transformative approach to CRC therapy. The concentration-responsive self-assembly of Pt(IV)-Cro NPs and the occurrence of morphologic transformations within the cell characterize a major advancement in clinical CRC therapeutic strategies.

Approaches that add value to biomass through the use of photoreforming reactions offer great opportunities for the efficient use of renewable resources. Here, we constructed a novel zinc cadmium sulphide/molybdenum dioxide-molybdenum carbide-carbon (ZnxCd1-xS-y/MoO2-Mo2C-C) heterojunction which was applied to photoreforming of biomass-based monosaccharides for hydrogen and lactic acid production. Bandgap engineering effectively modulated the redox capacity of ZnxCd1-xS-y and exposed more (101) crystalline surfaces, which improved the lactic acid selectivity. The MoO2-Mo2C-C (MC) co-catalysts had unique microstructures that increased the light absorption range and the number of active sites of ZnxCd1-xS-y. These features effectively promoted the separation and migration of photogenerated carriers, which in turn enhanced the photoreforming activity. The optimised Zn0.4Cd0.6S-0/MC composites exhibited superior photocatalytic activity with a hydrogen yield of 12.2 mmol/g/h. Conversion of biomass-based monosaccharides was approximately 100 %, where arabinose had the greatest lactic acid selectivity (64.1 %). Active species, including h+, center dot O2- , center dot OH, and 1O2, all favoured lactic acid production, where center dot O2- played a major role in the conversion. This study demonstrates that rational design of photocatalysts can achieve the selective conversion of biomass into high value-added chemicals as well as the generation of clean energy.

Enzyme-catalyzed transformation of vegetable oils into epoxidized vegetable oils (EVOs) is of significant importance for sustainable and green industrial production. However, challenges such as enzyme inactivation, low efficiency, and poor stability hinder its large-scale implementation. In this study, a continuous-flow catalytic system based on enzyme-encapsulated Pickering emulsion microcapsules was developed to address these issues. Candida antarctica lipase B (CALB) was encapsulated within microcapsules featuring porous silica shells, forming a stable aqueous microenvironment that maintains enzyme conformation and activity. This design also prevents droplet agglomeration and ensures stability in polar reaction media. By adjusting the structure of microcapsules and reaction conditions, including microcapsules size, shells thickness, enzyme content, and hydrogen peroxide concentration, the optimal conditions for the epoxidation reaction are identified. Utilizing these conditions, the system achieved 80%-92% conversion for the epoxidation of various vegetable oils, maintained long-term operational stability for up to 700 h, and exhibited a fivefold increase in specific activity compared to traditional batch systems. This study provides a novel and industrially viable approach to the epoxidation reaction of vegetable oils.

Hypoxia is a key reason for the failure of liver cancer therapy. Emerging evidences indicated that ROS played a crucial role in the sorafenib therapy, and overcoming the reduction in intracellular ROS levels was the first requirement for therapy resistance. Ubiquilin1 (UBQLN1) acted as an oncogene or suppressor gene involved in the protein degradation and abnormal protein aggregation. In this study, we proposed a novel strategy to reverse the hypoxia-induced resistance in liver cancer by isoliensinine (Iso), a significant bioactive compound derived from lotus seed. Based on preliminary screening, we found a significant elevation of UBQLN1 in liver cancer tissues obtained from the TCGA databases and in liver cancer cells under hypoxic model, which contributed to hypoxia-induced sorafenib resistance. Further data suggested that Iso significantly reversed the hypoxia-induced sorafenib resistance through directly targeting UBQLN1 and inducing ROS production. Notably, the ROS elevation induced by Iso could trigger IRP2-induced ferroptosis but remained below the threshold for mitochondrial damage in liver cancer cells. The related mechanism was that Iso reduced the binding between PGC1α and ubiquitin, promoting the stability of the PGC1α protein, which might accelerate mitochondrial energy metabolism. Taken together, our findings not only revealed that UBQLN1 played a critical role in ROS regulation, but also uncovered a previously unrecognized reversal mechanism of Iso in liver cancer, which promoted sensitization of sorafenib-induced ferroptosis by inhibition of UBQLN1/PGC1α pathway under hypoxia.