Investigating the role of non-ionic surfactants as electrolyte additives for improved zinc anode performance in aqueous batteries.

Zinc metal anodes encounter significant challenges, including dendrite growth, hydrogen evolution, and corrosion, all of which impede the rate capability and longevity of aqueous zinc-ion batteries (AZIBs). To effectively tackle these issues, we introduced Tween-80 into the traditional ZnSO4 electrolyte as an additive. Tween-80 possesses electronegative oxygen atoms that enable it to adsorb onto the zinc (Zn) anode surface, facilitating the directional deposition of Zn metal along the (002) orientation. The hydroxyl and ether groups within Tween-80 can displace some of the coordinated water molecules in the Zn2+ inner solvation shell. This disruption of the hydrogen bond network regulates the solvation structure of Zn2+ ions and suppresses the possibility of hydrogen evolution. Moreover, the long hydrocarbon chain present in Tween-80 exhibits excellent hydrophobic properties, aiding in the resistance against corrosion of the Zn anode by water molecules and reducing hydrogen evolution. Consequently, a symmetric cell equipped with the Tween-80 additive can cycle stably for over 4000 h at 1 mA cm-2 and 1 mA h cm-2. When paired with the V2O5 cathode, the full cell demonstrates a high-capacity retention rate exceeding 80 % over 1000 cycles at a current density of 2 A g-1. This study underscores the advantages of utilizing non-ionic surfactants for achieving high-performance aqueous zinc-ion batteries.

The evolution of cutinase Est1 based on the clustering strategy and its application for commercial PET bottles degradation.

The rapid increase in global plastic consumption, especially the worldwide use of polyethylene terephthalate (PET), has caused serious pollution problems. Due to the low recycling rate of PET, a substantial amount of waste accumulates in the environment, which prompts a growing focus on enzymatic degradation for its efficiency and environmentally friendliness. This study systematically designed and modified a cutinase, Est1 from Thermobifida alba AHK119, known for its potential of plastic-degradation at high temperatures. Additionally, the introduction of clustering algorithms provided the ability to understand and modify biomolecules, to accelerate the process of finding the optimal mutations. K-means was further proceeded based on the positive mutations. After comprehensive screening for thermostability and activity mutation sites, the dominant mutation Est1_5M (Est1 with the mutations of N213M, T215P, S115P, Q93A, and L91W) exhibited satisfying degradation ability for commercial PET bottles. The results showed that Est1_5M achieved a degradation rate of 90.84% in 72 h, 65-fold higher than the wild type. This study offers reliable theoretical and practical support for the development of efficient PET-degrading enzymes, providing a reference for plastic pollution management.

LncRNA NONHSAT227443.1 Confers Esophageal Squamous Cell Carcinoma Chemotherapy Resistance by Activating PI3K/AKT Signaling via Targeting MRTFB.

INTRODUCTION: Esophageal cancer presents significant challenges due to limited treatment options and poor prognosis, particularly in advanced stages. Dysregulated long non-coding RNAs (lncRNAs) are implicated in cancer progression and treatment resistance. This study investigated the roles of dysregulated lncRNA NONHSAT227443.1, identified through lncRNA-seq, and its downstream target gene MRTFB in esophageal squamous cell carcinoma (ESCC). METHODS: Dysregulated lncRNAs were identified through lncRNA-seq in esophageal cancer tissues with varying chemotherapy response. The regulatory interaction of overexpressed NONHSAT227443.1 was assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Functional assays, including cell viability, cell proliferation, and flow cytometry analyses, were performed to comprehensively investigate the influence of NONHSAT227443.1 and its downstream molecules on ESCC. RESULTS: NONHSAT227443.1 was significantly overexpressed in paclitaxel plus platinum chemotherapy non-responders and esophageal cancer cell lines. Chemotherapy exposure led to diminished NONHSAT227443.1 expression. NONHSAT227443.1 negatively regulated MRTFB expression, and their combined dysregulation correlated with increased cancer activity, proliferation, and suppressed apoptosis. Diminished MRTFB expression was associated with PI3K/AKT pathway activation. CONCLUSION: Our study provides insights into NONHSAT227443.1 and MRTFB roles in esophageal cancer, contributing to aggressive traits and treatment resistance. NONHSAT227443.1 and MRTFB may serve as potential therapeutic targets to enhance the response to paclitaxel plus platinum chemotherapy in non-responsive cases.

Correlation Between the Number of Pathological Risk Factors and Postoperative Prognosis in Patients with Stage I Lung Adenocarcinoma.

BACKGROUND: Although visceral pleural invasion, lymphovascular invasion, tumor spread through air spaces, and poor differentiation are pathological risk factors associated with unfavorable prognosis in patients with lung adenocarcinoma, the cumulative impact of these factors on prognosis remains unclear. METHODS: We enrolled 1532 patients with stage I lung adenocarcinoma. Patients were divided according to the number of risk factors as follows: Group A (without risk factors), Group B (one risk factor), and Group C (multiple risk factors). Moreover, we stratified patients into two subgroups based on tumor size (≤ 3 cm, 3-4 cm). Kaplan-Meier analysis was used to evaluate 5-year disease-free survival (DFS) and overall survival (OS). RESULTS: Overall, 949, 404, and 179 patients were included in Groups A, B, and C, respectively. Group C had a larger tumor size and more cases of extrathoracic recurrence than the other groups. The 5-year DFS and OS gradually decreased across Groups A to C (DFS: 94.3%, 80.6%, and 64.3%, respectively, p < 0.001; OS: 97.2%, 92.7%, and 77%, respectively, p < 0.001). A similar trend was observed for tumors ≤ 3 cm in size (DFS: 95.2%, 83.2%, and 68.5%, respectively, p < 0.001; OS: 97.6%, 94.1%, and 79.6%, respectively, p < 0.001), but a less pronounced trend was observed for tumors between 3 and 4 cm in size (DFS: 72.1, 60.8, and 43.3%, respectively, p = 0.054; OS: 85.7, 82.1, and 64.7%, respectively, p = 0.16). CONCLUSIONS: Postoperative survival worsened with increasing pathological risk factors in patients with stage I lung adenocarcinoma, especially those with tumor size ≤ 3 cm.

A self-bonding conductive electrode triggered by water-induced structure reconfiguration.

This study presents a self-bonding conductive electrode triggered by water-induced structure reconfiguration. Water wetting causes the swelling and mobility of cotton-derived cellulose nanofibers in the conductive electrode, and the formation of hydrogen bonds, which enables the conductive electrode to heal damage, bond separated pieces, and directly bond on diverse substrates.

Habitat for Coilia nasus in southern Zhejiang Province, China, based on a maximum entropy model.

As an important fishery resource and endangered species, studying the habitat of Coilia nasus (C. nasus) is highly significant. This study used fishery survey data from southern Zhejiang coastal waters from 2016 to 2020, employing a maximum entropy model (MaxEnt) to map the habitat distribution of C. nasus. Model performance was evaluated using two metrics: the area under the curve (AUC) of the receiver operating characteristic curve for the training and test sets and true skill statistics (TSS). This study aimed to predict the habitat distribution of C. nasus and explore how environmental variables influence habitat suitability. The results indicated that the models for each season had strong predictive performance, with AUC values above 0.8 and TSS values exceeding 0.6, indicating that they could accurately predict the presence of C. nasus. In the study area, C. nasus was primarily found in brackish or marine waters near bays and coastal islands. Among all environmental factors, salinity (S) and bottom temperature (BOT) had the highest correlations with habitat distribution, although these correlations varied across seasons. The findings of this study provide empirical evidence and a reference for the conservation and management of C. nasus and for the designation of its protected areas.

Understanding and manipulating the recognition of necrosis-inducing secreted protein 1 (NIS1) by BRI1-associated receptor kinase 1 (BAK1).

Necrosis-inducing secreted protein 1 (NIS1) is a core effector of Ascomycota and Basidiomycota fungi. They inhibit the immune responses of host plants mainly through interaction with the multi-functional coreceptor BRI1-associated receptor kinase 1 (BAK1). However, the structural mechanism of the NIS1 family and how they are recognized by BAK1 are unknown. Herein, we report the first crystal structure of the NIS1 family protein, the Magnaporthe oryzae NIS1 (MoNIS1), analyze the recognition mechanism of NIS1s by BAK1, and explore regulation of the NIS1-BAK1 interaction by a chemical compound. MoNIS1 exists as a ß barrel formed by eight ß strands, a folding mode that has not been reported. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) assay suggested that ß4-ß5 loop and ß5 strand of MoNIS1 participate in OsBAK1 interaction, which was supported by further single-point mutational assays. For OsBAK1, HDX-MS assay suggested four regions involved in MoNIS1 interaction. Additionally, we identified a compound that blocks MoNIS1-OsBAK1 interaction in vitro and inhibits the virulence of M. oryzae on rice. Collectively, we determined the first structure of NIS1 family effectors, presented the recognition mechanism of NIS1 by BAK1, and showed that blocking NIS1-BAK1 interaction could be a new target for fungicide development.

Electroacupuncture and methotrexate cooperate to ameliorate psoriasiform skin inflammation by regulating the immune balance of Th17/Treg.

Psoriasis is an autoinflammatory dermatosis, while methotrexate (MTX) is an immunosuppressant used to treat psoriasis. However, conventional immunosuppressants may cause various side effects. Acupuncture has potential benefits in treating psoriasis based on its anti-inflammatory effects. However, the immune mechanisms underlying its effects remain unclear. In this study, imiquimod-induced psoriatic mice were used to investigate the effects and mechanisms of electroacupuncture (EA) and, in particular, its joint treatment with MTX. We found that treatment with either EA or MTX ameliorated psoriasiform skin lesions, improved skin pathology and reduced proinflammatory cytokines in the skin, while joint treatment with both EA and MTX further alleviated the skin lesions and inflammation compared to either one alone. Moreover, percentages of CD4+ IL-17A+ Th17 cells in the skin and lymph nodes were decreased by EA or MTX and further lowered by combined EA+MTX treatment. Similarly, EA or MTX also reduced their RORγt expression. On the contrary, CD4+ FoxP3+ Treg frequency in psoriatic mice was augmented by EA or MTX and further increased by the joint treatment. However, depleting Tregs mostly reversed the therapeutic effects of EA or EA plus MTX. Additionally, the phosphorylated NF-κB (p65) expression was suppressed by treatment with EA, MTX or better with EA+MTX. Meanwhile, the anti-inflammatory effects of EA plus MTX were offset by an NF-κB agonist. Thus, this study has revealed that EA cooperates with MTX to balance Th17/Treg responses and to ameliorate psoriasiform skin inflammation through suppressing NF-κB activation. Our findings may be implicated for treating human psoriasis.

Periodic Single-Metal Site Catalysts: Creating Homogeneous and Ordered Atomic-Precision Structures.

Heterogeneous single-metal-site catalysts (SMSCs), often referred to as single-atom catalysts (SACs), demonstrate promising catalytic activity, selectivity, and stability across a wide spectrum of reactions due to their rationally designed microenvironments encompassing coordination geometry, binding ligands, and electronic configurations. However, the inherent disorderliness of SMSCs at both atomic scale and nanoscale poses challenges in deciphering working principles and establishing the correlations between microenvironments and the catalytic performances of SMSCs. The rearrangement of randomly dispersed single metals into homogeneous and atomic-precisely structured periodic single-metal site catalysts (PSMSCs) not only simplifies the chaos in SMSCs systems but also unveils new opportunities for manipulating catalytic performance and gaining profound insights into reaction mechanisms. Moreover, the synergistic effects of adjacent single metals and the integration effects of periodic single-metal arrangement further broaden the industrial application scope of SMSCs. This perspective offers a comprehensive overview of recent advancements and outlines prospective avenues for research in the design and characterizations of PSMSCs, while also acknowledging the formidable challenges encountered and the promising prospects that lie ahead.

Long-Term Stable Dispersion of Multiwalled Carbon Nanotubes by Peroxydisulfate upon Ultrasonication Activation.

Poor dispersibility of carbon nanotubes greatly hinders their practical applications. Herein, a long-term stable dispersion of multiwalled carbon nanotubes (MWCNTs) in peroxydisulfate (PDS) is achieved. MWCNTs at 40 mg L-1 are completely dispersed by PDS upon ultrasonication (US/PDS) within 64 min and a stable dispersion is maintained at least 20 days. Mechanistically, US created defects on the nanomaterial and PDS-origin free radicals attacked these defects to introduce O-containing moieties (─OH and ─COOH). Interestingly, dispersion efficiency of MWCNTs by US/PDS initially at pH 7 and 3.8 is comparable, but lower than that initially at pH 12. Both •OH and SO4 •- are produced under alkaline condition, while SO4 •- is the dominant free radicals initially at pH 7 and 3.8 during the whole dispersion period. Stronger dispersion of MWCNTs initially at pH 12 resulted from greater amounts of O-containing moieties mainly in ─OH (46.32%) rather than ─COOH (24.19%) form. This differential more strongly promotes MWCNTs-water interaction via hydrogen bonding, thereby enhancing the dispersion. Notably, no significant mass loss of MWCNTs occurred during dispersion. Overall, the developed method achieves long-term stable dispersion of MWCNTs in a manner that can significantly extend their applications.

Exosomal Src from hypoxic vascular smooth muscle cells exacerbates ischemic brain injury by promoting M1 microglial polarization.

Inflammatory response mediated by M1 microglia is a crucial factor leading to the exacerbation of brain injury after ischemic stroke (IS). Under the stimulation of IS, vascular smooth muscle cells (VSMCs) switch to the synthetic phenotype characterized by exosome secretion. Previous studies have shown that exosomes play an important role in the regulation of microglial polarization. We reported that exosomes derived from primary human brain VSMCs under hypoxia (HExos), but not those under normoxia (Exos), significantly promoted primary human microglia (HM1900) shift to M1 phenotype. Proteomic analysis showed that the Src protein enriched in HExos was a potential pro-inflammatory mediator. In vitro experiments showed that the expression of Src and M1 markers were upregulated in HM1900 co-incubated with HExos. However, the Src inhibitor dasatinib (DAS) significantly promoted the transformation of HM1900 phenotype from M1 to M2. In vivo experiments of pMCAO mice also revealed that DAS could effectively inhibit the activation of M1 microglia/macrophages, protect neurons from apoptosis, and improve neuronal function. These data suggested that hypoxic-VSMCs-derived exosomes were involved in post-IS inflammation by promoting M1 microglial polarization through Src transmission. Targeting inhibition of Src potentially acts as an effective strategy for treating brain injury after IS.

Changes in the recent three decades and survey on the current status of surgical treatment for esophageal cancer in China.

BACKGROUND: To review the changes and survey on status quo of the surgical treatment for esophageal cancer in China. The differences in diagnosis and treatment for esophageal cancer among hospitals in different regions across China were also investigated. METHODS: We sent questionnaires to 46 hospitals across China, investigating the volume of esophageal cancer surgeries, surgical procedures, and perioperative management under the guidance of esophageal surgery chiefs. RESULTS: A total of 46 questionnaires were sent out and collected. The survey results showed that in the past 5 years, the volume of surgeries for esophageal cancer remained stable by 23.9% of those hospitals, increased by 30.4%, and decreased by 45.7%. Of those patients treated by surgery, 19.1% were in the early stages, and 80.9% were in locally advanced stages. In terms of surgical procedures, 73.4% of the patients were treated by minimally invasive surgery and 85.7% of esophageal substitutes were a gastric conduit, 93.1% of the substitutes were pulled to the neck through the esophageal bed. For the lymph node dissection, 78.5% of the patients had a complete two-field lymph node dissection including the para-recurrent laryngeal nerve lymph nodes. Of the patients with neoadjuvant therapy, 53.5% received chemotherapy or chemotherapy plus immunotherapy (47.0%), and 43.5% had chemoradiation. CONCLUSIONS: Currently, in China, minimally invasive surgery-oriented multimodality treatment, including complete two-field lymph node dissection, has become the standard approach for esophageal cancer management. Over the past decade, this standardized approach has significantly improved prognosis compared to previous decades.

Applications of nanotechnology in orthodontics: a comprehensive review of tooth movement, antibacterial properties, friction reduction, and corrosion resistance.

Nanotechnology has contributed important innovations to medicine and dentistry, and has also offered various applications to the field of orthodontics. Intraoral appliances must function in a complex environment that includes digestive enzymes, a diverse microbiome, mechanical stress, and fluctuations of pH and temperature. Nanotechnology can improve the performance of orthodontic brackets and archwires by reducing friction, inhibiting bacterial growth and biofilm formation, optimizing tooth remineralization, improving corrosion resistance and biocompatibility of metal substrates, and accelerating or decelerating orthodontic tooth movement through the application of novel nanocoatings, nanoelectromechanical systems, and nanorobots. This comprehensive review systematically explores the orthodontic applications of nanotechnology, particularly its impacts on tooth movement, antibacterial activity, friction reduction, and corrosion resistance. A search across PubMed, the Web of Science Core Collection, and Google Scholar yielded 261 papers, of which 28 met our inclusion criteria. These selected studies highlight the significant benefits of nanotechnology in orthodontic devices. Recent clinical trials demonstrate that advancements brought by nanotechnology may facilitate the future delivery of more effective and comfortable orthodontic care.

Bio-accessibility and bio-availability evaluation of each arsenic species existing in various edible seaweeds in vitro and in vivo for arsenic risk assessment.

Seaweeds consumption is one of main internal exposure sources of arsenic for human. However, the absence of representative bio-availabilities of arsenic species makes the accurate assessment of arsenic health risk originating from seaweeds consumption impossible. Herein, the arsenic species in various seaweeds collected from Fujian of China were investigated, and the bio-accessibilities/bio-availabilities of arsenic species existing in seaweeds were evaluated in vitro and in vivo. Results revealed that in vitro bio-availabilities of arsenic species presenting in seaweeds, which obtained with Caco-2 cells, were lower than those of pure arsenic standards, and varied with order of inorganic arsenic (iAs) > dimethylarsinic acid (DMA) ≈ arsenobetaine (AsB) > arsenosugars. During gastrointestinal digestion of mice, As5+ was partly methylated into monomethylarsonic acid (MMA) and DMA, which makes the in vivo bioavailability of iAs (⁓31.8 %) obtained with mouse metabolic experiment is much higher than its in vitro bio-availability (⁓10.3 %). The in vivo bio-availabilities of DMA and total arsenic (tAs) are similar to their in vitro bio-availabilities. As the dominant arsenic species in most seaweeds, arsenosugars have an ⁓0.0 % of in vivo bioavailability and only a ⁓3.7 % of in vitro bioavailability. The simulated calculation of target hazard quotient (THQ) and target cancer risk (TR) revealed that the arsenic risk originating from seaweeds was greatly degraded by taking into consideration of arsenic species and bio-availabilities, and all seaweeds collected from Fujian are safety for consumption. The simulated calculation also revealed that arsenic risk of seaweeds can be also more accurately assessed based on tAs together with bioavailability, which provides a simple but accurate and protective method for the risk assessment of arsenic originating from seaweeds. Our work provides the possible representative bio-availabilities of arsenic species presenting in seaweeds for accurately assessing arsenic risk of seaweeds, and novel insights into the bio-availabilities of arsenic in animal.

Two distinct archaeal type IV pili structures formed by proteins with identical sequence.

Type IV pili (T4P) represent one of the most common varieties of surface appendages in archaea. These filaments, assembled from small pilin proteins, can be many microns long and serve diverse functions, including adhesion, biofilm formation, motility, and intercellular communication. Here, we determine atomic structures of two distinct adhesive T4P from Saccharolobus islandicus via cryo-electron microscopy (cryo-EM). Unexpectedly, both pili were assembled from the same pilin polypeptide but under different growth conditions. One filament, denoted mono-pilus, conforms to canonical archaeal T4P structures where all subunits are equivalent, whereas in the other filament, the tri-pilus, the same polypeptide exists in three different conformations. The three conformations in the tri-pilus are very different from the single conformation found in the mono-pilus, and involve different orientations of the outer immunoglobulin-like domains, mediated by a very flexible linker. Remarkably, the outer domains rotate nearly 180° between the mono- and tri-pilus conformations. Both forms of pili require the same ATPase and TadC-like membrane pore for assembly, indicating that the same secretion system can produce structurally very different filaments. Our results show that the structures of archaeal T4P appear to be less constrained and rigid than those of the homologous archaeal flagellar filaments that serve as helical propellers.

A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease.

BACKGROUND: With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11. METHODS: Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members. RESULTS: A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p = 0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%). CONCLUSIONS: This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.

Isolation of aptamers with excellent cross-reactivity and specificity to sulfonamides towards a ratiometric fluorescent aptasensor for the detection of nine sulfonamides in seafood.

Sulfonamides (SAs) is a class of antibiotics that extensively used for treating infectious diseases in livestock industries and aquaculture. Thus, it is urgent need to obtain the bio-receptor, which has excellent cross-reactivity and specificity to SAs, for developing high-throughput methods for the determination of multiple SAs even all commonly-used SAs, to realize the quick screening/detection of total SAs in animal-derived foods. We herein isolated several SAs-specific cross-reactive aptamers by using a library-immobilized SELEX with multi-SAs parallel selection strategy. Two of the isolated aptamers (Sul-01 and Sul-04) can specifically recognize and bind seven SAs respectively with higher binding affinity and no interference of non-sulfonamide antibiotics, and thus can be applied as bio-receptors for developing high-throughput aptasensors for the quick screening/detection of multiple SAs. By using the mixture of Sul-01 and Sul-04 as bio-receptor, a ratiometric fluorescent aptasensor was created for the quick detection of nine SAs including sulfamethoxydiazine (SMD), sulfapyridine (SPD), sulfaquinoxaline (SQ), sulfathiazole (ST), sulfamonomethoxine (SMM), sulfamerazine (SMR), sulfaguanidine (SG), sulfamethazine (SMZ) and sulfadiazine (SD) with a detection limit (LOD) of 0.10-0.50 µM, or total of above nine SAs with a LOD of 0.20 µM. The fluorescent aptasensor was successfully applied to detect each or total of SMD, SPD, SQ, ST, SMM, SMR, SG, SMZ and SD in fish samples with a recovery of 83 %-92 % and a relative standard deviation (RSD, n = 5) < 5 %. This study not only provided several promising bio-receptors for the development of diverse high-throughput aptasensors to achieve the quick screening of multiple SAs residues, but also provided a simple, stable and sensitive method for the quick screening of SMD, SPD, SQ, ST, SMM, SMR, SG, SMZ and SD in seafood.

Targeting SUMOylation with an injectable nanocomposite hydrogel to optimize radiofrequency ablation therapy for hepatocellular carcinoma.

BACKGROUND: Incomplete radiofrequency ablation (iRFA) in hepatocellular carcinoma (HCC) often leads to local recurrence and distant metastasis of the residual tumor. This is closely linked to the development of a tumor immunosuppressive environment (TIME). In this study, underlying mechanisms and potential therapeutic targets involved in the formation of TIME in residual tumors following iRFA were explored. Then, TAK-981-loaded nanocomposite hydrogel was constructed, and its therapeutic effects on residual tumors were investigated. RESULTS: This study reveals that the upregulation of small ubiquitin-like modifier 2 (Sumo2) and activated SUMOylation is intricately tied to immunosuppression in residual tumors post-iRFA. Both knockdown of Sumo2 and inhibiting SUMOylation with TAK-981 activate IFN-1 signaling in HCC cells, thereby promoting dendritic cell maturation. Herein, we propose an injectable PDLLA-PEG-PDLLA (PLEL) nanocomposite hydrogel which incorporates self-assembled TAK-981 and BSA nanoparticles for complementary localized treatment of residual tumor after iRFA. The sustained release of TAK-981 from this hydrogel curbs the expansion of residual tumors and notably stimulates the dendritic cell and cytotoxic lymphocyte-mediated antitumor immune response in residual tumors while maintaining biosafety. Furthermore, the treatment with TAK-981 nanocomposite hydrogel resulted in a widespread elevation in PD-L1 levels. Combining TAK-981 nanocomposite hydrogel with PD-L1 blockade therapy synergistically eradicates residual tumors and suppresses distant tumors. CONCLUSIONS: These findings underscore the potential of the TAK-981-based strategy as an effective therapy to enhance RFA therapy for HCC.