General synthesis of high-entropy single-atom nanocages for electrosynthesis of ammonia from nitrate.

Given the growing emphasis on energy efficiency, environmental sustainability, and agricultural demand, there's a pressing need for decentralized and scalable ammonia production. Converting nitrate ions electrochemically, which are commonly found in industrial wastewater and polluted groundwater, into ammonia offers a viable approach for both wastewater treatment and ammonia production yet limited by low producibility and scalability. Here we report a versatile and scalable solution-phase synthesis of high-entropy single-atom nanocages (HESA NCs) in which Fe and other five metals-Co, Cu, Zn, Cd, and In-are isolated via cyano-bridges and coordinated with C and N, respectively. Incorporating and isolating the five metals into the matrix of Fe resulted in Fe-C5 active sites with a minimized symmetry of lattice as well as facilitated water dissociation and thus hydrogenation process. As a result, the Fe-HESA NCs exhibited a high selectivity toward NH3 from the electrocatalytic reduction of nitrate with a Faradaic efficiency of 93.4% while maintaining a high yield rate of 81.4 mg h-1 mg-1.

Metal Artifacts Reducing Method Based on Diffusion Model Using Intraoral Optical Scanning Data for Dental Cone-beam CT.

In dental cone-beam computed tomography (CBCT), metal implants can cause metal artifacts, affecting image quality and the final medical diagnosis. To reduce the impact of metal artifacts, our proposed metal artifacts reduction (MAR) method takes a novel approach by integrating CBCT data with intraoral optical scanning data, utilizing information from these two different modalities to correct metal artifacts in the projection domain using a guided-diffusion model. The intraoral optical scanning data provides a more accurate generation domain for the diffusion model. We have proposed a multi-channel generation method in the training and generation stage of the diffusion model, considering the physical mechanism of CBCT, to ensure the consistency of the diffusion model generation. In this paper, we present experimental results that convincingly demonstrate the feasibility and efficacy of our approach, which introduces intraoral optical scanning data into the analysis and processing of projection domain data using the diffusion model for the first time, and modifies the diffusion model to better adapt to the physical model of CBCT.

Asymmetric bifunctionalization of allenes with aryl iodides and amino acids enabled by chiral aldehyde/palladium combined catalysis.

Even though catalytic asymmetric bifunctionalization of allenes has been extensively studied, almost all of the reported examples have been achieved in a two-component manner. In this study, we report a highly efficient asymmetric bifunctionalization of allenes with iodohydrocarbons and NH2-unprotected amino acid esters. The adopted chiral aldehyde/palladium combined catalytic system precisely governs the chemoselectivity, regioselectivity, and stereoselectivity of this three-component reaction. A wide range of substituted aryl iodides, allenes and amino acid esters can well participate in this reaction and deliver structurally diverse α,α-disubstituted α-amino acid esters with excellent experimental outcomes. One of the resulting products is utilized for the total synthesis of the molecule (S,R)-VPC01091.

Evolutionary game analysis between regional governments and shipping companies: Considering the impact of government subsidy on shipping companies.

Maritime agencies are imposing stricter limits on fuel sulfur content, and regional governments are encouraging the reduction of various emissions through subsidies. In this study, an evolutionary game model is constructed to analyze the interaction between regional governments and shipping companies under the fixed and dynamic subsidies. The sensitivity analysis reveals the effect of parameters on stabilization strategies. The results show that the bilateral stakeholders can adopt stabilization strategies under dynamic subsidies. The fines, maximum subsidies and extra cost paid by regional governments have a significant impact on these strategies. To reduce the dependence of shipping companies on subsidy policies, it is recommended to improve the LSFO refining technology in the future. Expanding the implementation scope of LSFO subsidy policies will increase the utilization of LSFO by shipping companies. This study offers insights for governments to optimize the LSFO subsidy policy and shipping companies to choose sulfur oxides reduction approaches.

SCA44- and SCAR13-associated GRM1 mutations affect metabotropic glutamate receptor 1 function through distinct mechanisms.

BACKGROUND AND PURPOSE: Metabotropic glutamate receptor 1 (mGlu1) is a promising therapeutic target for neurodegenerative CNS disorders including spinocerebellar ataxias (SCAs). Clinical reports have identified naturally-occurring mGlu1 mutations in rare SCA subtypes and linked symptoms to mGlu1 mutations. However, how mutations alter mGlu1 function remains unknown, as does amenability of receptor function to pharmacological rescue. Here, we explored SCA-associated mutation effects on mGlu1 cell surface expression, canonical signal transduction and allosteric ligand pharmacology. EXPERIMENTAL APPROACH: Orthosteric agonists, positive allosteric modulators (PAMs) and negative allosteric modulators (NAMs) were assessed at two functional endpoints (iCa2+ mobilisation and inositol 1-phosphate [IP1] accumulation) in FlpIn Trex HEK293A cell lines expressing five mutant mGlu1 subtypes. Key pharmacological parameters including ligand potency, affinity and cooperativity were derived using operational models of agonism and allostery. KEY RESULTS: mGlu1 mutants exhibited differential impacts on mGlu1 expression, with a C-terminus truncation significantly reducing surface expression. Mutations differentially influenced orthosteric ligand affinity, efficacy and functional cooperativity between allosteric and orthosteric ligands. Loss-of-function mutations L454F and N885del reduced orthosteric affinity and efficacy, respectively. A gain-of-function Y792C mutant mGlu1 displayed enhanced constitutive activity in IP1 assays, which manifested as reduced orthosteric agonist activity. The mGlu1 PAMs restored glutamate potency in iCa2+ mobilisation for loss-of-function mutations and mGlu1 NAMs displayed enhanced inverse agonist activity at Y792C relative to wild-type mGlu1. CONCLUSION AND IMPLICATIONS: Collectively, these data highlight distinct mechanisms by which mGlu1 mutations affect receptor function and show allosteric modulators may present a therapeutic strategy to restore aberrant mGlu1 function in rare SCA subtypes.

E3 Ubiquitin Ligase RNF13 Suppresses TLR Lysosomal Degradation by Promoting LAMP-1 Proteasomal Degradation.

As a highly organized system, endo-lysosomes play a crucial role in maintaining immune homeostasis. However, the mechanisms involved in regulating endo-lysosome progression and subsequent inflammatory responses are not fully understood. By screening 103 E3 ubiquitin ligases in regulating endo-lysosomal acidification, it is discovered that lysosomal RNF13 inhibits lysosome maturation and promotes inflammatory responses mediated by endosomal Toll-like receptors (TLRs) in macrophages. Mechanistically, RNF13 mediates K48-linked polyubiquitination of LAMP-1 at residue K128 for proteasomal degradation. Upon TLRs activation, LAMP-1 promotes lysosomes maturation, which accelerates lysosomal degradation of TLRs and reduces TLR signaling in macrophages. Furthermore, peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis (RA) show increased RNF13 levels and decreased LAMP-1 expression. Accordingly, the immunosuppressive agent hydroxychloroquine (HCQ) can increase the polyubiquitination of RNF13. Taken together, the study establishes a linkage between proteasomal and lysosomal degradation mechanisms for the induction of appropriate innate immune response, and offers a promising approach for the treatment of inflammatory diseases by targeting intracellular TLRs.

Arabidopsis WRKY1 promotes monocarpic senescence by integrative regulation of flowering, leaf senescence, and nitrogen remobilization.

Monocarpic senescence, characterized by whole-plant senescence following a single flowering phase, is widespread in seed plants, particularly in crops, determining seed harvest time and quality. However, how external and internal signals are systemically integrated into monocarpic senescence remains largely unknown. Here, we report that the Arabidopsis thaliana transcription factor WRKY1 plays essential roles in multiple key steps of monocarpic senescence. WRKY1 expression is induced by age, salicylic acid (SA), and nitrogen (N) deficiency. Flowering and leaf senescence are accelerated in the WRKY1 overexpression lines but are delayed in the wrky1 mutants. The combined DNA affinity purification sequencing and RNA sequencing analyses uncover the direct target genes of WRKY1. Further studies show that WRKY1 coordinately regulates three processes in monocarpic senescence: (1) suppressing FLOWERING LOCUS C gene expression to initiate flowering, (2) inducing SA biosynthesis genes to promote leaf senescence, and (3) activating the N assimilation and transport genes to trigger N remobilization. In summary, our study reveals how one stress-responsive transcription factor, WRKY1, integrates flowering, leaf senescence, and N remobilization processes into monocarpic senescence, providing important insights into plant lifetime regulation.

Establishment and verification of novel TNM staging system for lung mucinous adenocarcinoma.

BACKGROUND: Lung adenocarcinoma is a high-mortality rate cancer. Within this category, Lung mucinous adenocarcinoma (LMAC) is a rare and distinct subtype of lung adenocarcinoma necessitating further investigation. The study was launched to compare the difference of survival features between LMAC and lung non-mucinous adenocarcinoma (LNMAC) and to investigate the significance and demand for developing a new staging system tailored to LMAC. METHODS: This retrospective study assessed the suitableness of the current staging system for LMAC. It compared the overall survival (OS) between LMAC and LNMAC from 2004 to 2020 (LNMAC: 160,387; LMAC: 6,341) and instituted a novel classification framework for LMAC based on US population. Verification group consisting of patients from two Chinese medical centers from 2010 to 2018 (n = 392) was set to ascertain the applicability of this novel system. The primary endpoint was OS. To minimize the bias, propensity score match (PSM) was employed. Survival analysis and Log-rank test were executed to explore the survival features of LMAC. RESULTS: The results indicated that the existed staging system was not suitable for LMAC. Patients diagnosed with LMAC exhibited a superior OS compared to those with LNMAC in stage IA2 (P < 0.0001), IA3 (P < 0.0001), IB (P = 0.0062), IIA (P = 0.0090), IIB (P = 0.0005). In contrast, a worse OS in stage IVA (P = 0.0103) was found in LMAC patients. The novel classification system proposed for LMAC proved to be highly applicable and demonstrated substantial efficacy, as confirmed by the verification group. CONCLUSION: The newly established classification system was more effective for LMAC, but it necessitates large-scale verification to confirm its applicability and reliability.

Low Barriers and Faster Electron/Ion Transport Rates through the Ga2O3/MnCO3 Anode with a Heterojunction Structure for Lithium-Ion Batteries.

Electrode stability can be controlled to a large extent by constructing suitable composite structures, in which the heterojunction structure can affect the transport of electrons and ions through the effect of the interface state, changed band gap width, and the electric field at the interface. As a promising electrode material, the Ga-based material has a conversion between solid and liquid phases in the electrochemical reaction process, which endows it with self-healing properties with the structure and morphology. Based on these, the Ga2O3/MnCO3 composite was successfully synthesized with a heterogeneous structure by introducing a Ga source in the hydrothermal process. Benefitting from the acceleration effect of the internal electric field and the narrower band gap at the interface, a high-capacity Ga2O3/MnCO3 composite electrode (1112 mAh·g-1 after 225 cycles at 0.1 A·g-1 and 457.1 mAh·g-1 after 400 cycles at 1 A·g-1) can be achieved for lithium-ion batteries. The results can provide a reference for the research and preparation of electrode materials with high performance.

Stratifying TAD boundaries pinpoints focal genomic regions of regulation, damage, and repair.

Advances in chromatin mapping have exposed the complex chromatin hierarchical organization in mammals, including topologically associating domains (TADs) and their substructures, yet the functional implications of this hierarchy in gene regulation and disease progression are not fully elucidated. Our study delves into the phenomenon of shared TAD boundaries, which are pivotal in maintaining the hierarchical chromatin structure and regulating gene activity. By integrating high-resolution Hi-C data, chromatin accessibility, and DNA double-strand breaks (DSBs) data from various cell lines, we systematically explore the complex regulatory landscape at high-level TAD boundaries. Our findings indicate that these boundaries are not only key architectural elements but also vibrant hubs, enriched with functionally crucial genes and complex transcription factor binding site-clustered regions. Moreover, they exhibit a pronounced enrichment of DSBs, suggesting a nuanced interplay between transcriptional regulation and genomic stability. Our research provides novel insights into the intricate relationship between the 3D genome structure, gene regulation, and DNA repair mechanisms, highlighting the role of shared TAD boundaries in maintaining genomic integrity and resilience against perturbations. The implications of our findings extend to understanding the complexities of genomic diseases and open new avenues for therapeutic interventions targeting the structural and functional integrity of TAD boundaries.

Nitrogen and Sulfur Co-doped Biomass-Derived Porous Carbon Electrodes for Ultra-High-Performance All-Aqueous Thermally Regenerative Flow Batteries.

Developing high-performance electrodes for the all-aqueous thermally regenerative ammonia battery (ATRB) system, serving as superior substitutes for commercial carbon cloth electrodes, is anticipated to enhance performance, yet it lacks effective guidance and research. In this work, theoretical analysis is initially used to evaluate the effective conversion and adsorption capacity of nitrogen and sulfur co-doped carbon with respect to copper ion by density functional theory calculation. On the basis of this concept, the nitrogen and sulfur co-doped biomass-derived porous carbon electrode (DGC) is prepared using natural porous carbon materials and thiourea. Compared with commercial carbon cloth electrodes, ATRB with DGC achieves a significant improvement in maximum power density of 49.2%. Via optimization of the doping conditions, the active sites can be effectively regulated to boost charge transfer at the reaction interface. Furthermore, the rapid charge transfer can match the excellent mass transfer performance, generating an impressive net power density of 847.5 W/m2.

Discovery of N-Substituted Acetamide Derivatives as Promising P2Y14R Antagonists Using Molecular Hybridization Based on Crystallographic Overlay.

P2Y14 receptor (P2Y14R) is activated by uridine 5'-diphosphate-glucose, which is involved in many human inflammatory diseases. Based on the molecular docking analysis of currently reported P2Y14R antagonists and the crystallographic overlap study between the reported P2Y14R antagonist compounds 6 and 9, a series of N-substituted-acetamide derivatives were designed, synthesized, and identified as novel and potent P2Y14R antagonists. The most potent antagonist, compound I-17 (N-(1H-benzo[d]imidazol-6-yl)-2-(4-bromophenoxy)acetamide, IC50 = 0.6 nM) without zwitterionic character, showed strong binding ability to P2Y14R, high selectivity, moderate oral bioactivity, and improved pharmacokinetic profiles. In vitro and in vivo evaluation demonstrated that compound I-17 had satisfactory inhibitory activity on the inflammatory response of monosodium urate (MSU)-induced acute gouty arthritis. I-17 decreased inflammatory factor release and cell pyroptosis through the NOD-like receptor family pyrin domain-containing 3 (NLRP3)/gasdermin D (GSDMD) signaling pathway. Thus, compound I-17, with potent P2Y14R antagonistic activity, in vitro and in vivo efficacy, and favorable bioavailability (F = 75%), could be a promising lead compound for acute gouty arthritis.

Metabolic Blockade-Based Genome Mining of Sea Anemone-Associated Streptomyces sp. S1502 Identifies Atypical Angucyclines WS-5995 A-E: Isolation, Identification, Biosynthetic Investigation, and Bioactivities.

Marine symbiotic and epiphyte microorganisms are sources of bioactive or structurally novel natural products. Metabolic blockade-based genome mining has been proven to be an effective strategy to accelerate the discovery of natural products from both terrestrial and marine microorganisms. Here, the metabolic blockade-based genome mining strategy was applied to the discovery of other metabolites in a sea anemone-associated Streptomyces sp. S1502. We constructed a mutant Streptomyces sp. S1502/Δstp1 that switched to producing the atypical angucyclines WS-5995 A-E, among which WS-5995 E is a new compound. A biosynthetic gene cluster (wsm) of the angucyclines was identified through gene knock-out and heterologous expression studies. The biosynthetic pathways of WS-5995 A-E were proposed, the roles of some tailoring and regulatory genes were investigated, and the biological activities of WS-5995 A-E were evaluated. WS-5995 A has significant anti-Eimeria tenell activity with an IC50 value of 2.21 µM. The production of antibacterial streptopyrroles and anticoccidial WS-5995 A-E may play a protective role in the mutual relationship between Streptomyces sp. S1502 and its host.

Anti-phasic oscillatory development for speech and noise processing in cochlear implanted toddlers.

Human brain demonstrates amazing readiness for speech and language learning at birth, but the auditory development preceding such readiness remains unknown. Cochlear implanted (CI) children (n = 67; mean age 2.77 year ± 1.31 SD; 28 females) with prelingual deafness provide a unique opportunity to study this stage. Using functional near-infrared spectroscopy, it was revealed that the brain of CI children was irresponsive to sounds at CI hearing onset. With increasing CI experiences up to 32 months, the brain demonstrated function, region and hemisphere specific development. Most strikingly, the left anterior temporal lobe showed an oscillatory trajectory, changing in opposite phases for speech and noise. The study provides the first longitudinal brain imaging evidence for early auditory development preceding speech acquisition.

The Role of Nutrition and Body Composition on Metabolism.

Metabolism encompasses the entire array of chemical reactions continuously occurring within the body that sustain life and maintain normal physiological functions [...].

The association between rapid growth and lipid profile: a systematic review and meta-analysis.

Background & aims: Metabolic disease prevalence has increased in many regions, and is closely associated with dyslipidemia. Rapid growth refers to a significant increase in growth velocity above the normal range, particularly in infants and children, and is highly prevalent in congenital deficiency infants. But the association between dyslipidemia and rapid growth remains controversial. We performed this meta-analysis to investigate the lipid profile in subjects with and without postnatal rapid growth, and to determine what are the confounding factors. Methods: Medline, EMBASE, China National Knowledge Infrastructure Chinese citation database and WANFANG database were searched (last search in May 2021). Publication bias was examined by constructing funnel plots, Egger's linear regression test and Begg's rank correlation test. Results: The fixed effects model would be adopted if I2 is less than 25%, otherwise random effects model would be used. There were 11 articles involved with a total of 1148 participants (539 boys and 609 girls, mean age=7.4 years). Pooled analysis found that rapid growth was negatively associated with high-density lipoprotein cholesterol (HDL-C) (weighted mean difference=-0.068, 95%CI [-0.117, -0.020]), but not associated with triglycerides (TG), total cholesterol (TC), or low-density lipoprotein cholesterol (LDL-C). Stratified analysis suggested that increased TG were found in rapid growth subjects from developing countries. Higher TC was observed for rapid growth participants of follow-up age ≤8 years old, rapid growth duration ≤2 years, preterm, low birth weight, and from developing countries. But decreased TC was observed in small for gestational age (SGA) rapid growth subjects. Decreased LDL-C had been documented in rapid growth subjects of follow-up age >8 years old, from developed countries, and SGA. At last, rapid growth groups had lower HDL-C in infants of rapid growth duration >2 years and from developed countries. Conclusion: Rapid growth is associated with lipid profiles, particularly during early childhood, and this relationship is influenced by factors such as the duration of growth, the level of national development, and birth weight. These findings are significant for the development of strategies to prevent metabolic diseases.This review was registered in PROSPERO International Prospective Register of Systematic Reviews (www.crd.york.ac.uk/prospero/) with the registration number CRD42020154240.

Bistable Electrochromic Ionogels via Supramolecular Interactions for Energy-Efficient Displays.

Bistable electrochromic (EC) materials and systems offer significant potential for building decarbonization through their optical modulation and energy efficiency. However, challenges such as limited design strategies and bottlenecks in cost, fabrication, and color have hindered the full commercialization of energy-saving EC windows and displays, with few materials achieving true bistability. Herein, a novel strategy for designing bistable electrochromic materials is proposed by leveraging supramolecular interactions. These interactions facilitate reversible color transitions, stabilize the colored structure, and enable spatial confinement to inhibit diffusion, thereby achieving bistable electrochromism. The mechanisms and materials underlying these unconventional electrochromic systems are substantiated through detailed characterization. This strategy enables the preparation of low-cost and sustainable transparent electrochromic displays with high performance. Notably, the display information remains clearly visible for more than 2 h without consuming energy. Involving biomass materials and removable device structures also enhances the sustainability and scalability of EC technology applications and development. These results demonstrate the crucial role of supramolecular chemistry in the development of cutting-edge materials for applications such as energy-saving smart windows.

Dynamics of carbon and water vapor fluxes in three typical ecosystems of Heihe River Basin, Northwestern China.

Understanding the dynamics of carbon and water vapor fluxes in arid inland river basin ecosystems is essential for predicting and assessing the regional carbon-water budget amid climate change. However, studies aiming to unravel the mechanisms driving the variations and coupling process of regional carbon-water budget in a changing environment in arid regions are limited. Here, we used the eddy covariance technique to analyze the relationship between CO2 and H2O fluxes in three typical ecosystems across the upper, middle, and lower reaches of an arid inland river basin in Northwestern China. Our results showed that all ecosystems acted as carbon sinks, with the alpine swamp meadow, cropland, and desert shrubland sequestrating -300.2 ± 0.01, -644.8 ± 2.9, and - 203.7 ± 22.5 g C m-2 yr-1, respectively. Air temperature (Ta) primarily controlled daily gross primary productivity (GPP) and net ecosystem CO2 exchange (NEE) in the irrigated cropland during the growing season, while soil temperature (Ts) and vapor pressure deficit (VPD) regulated these parameters in the alpine swamp meadow and desert shrubland. Additionally, Ta and net radiation (Rn) controlled daily evapotranspiration (ET) in cropland, while Ts and Rn regulated ET at other sites. Consequently, carbon and water vapor fluxes of all three ecosystems tended to be energy-limited during the growing season. The differential responses of carbon and water vapor fluxes in the upper, middle, and lower reaches of these ecosystems to biophysical factors determined their distinct coupling and variations in water use efficiency. Notably, the desert shrub ecosystem in the lower reach of the basin maintained a stable balance between carbon gain and water loss, indicating adaptation to aridity. This study provides valuable insights into the underlying mechanisms behind the changes in carbon and water vapor fluxes and water-use efficiency in arid river basin ecosystems.

Sustainable, low-cost, high-contrast electrochromic displays via host-guest interactions.

Electrochromic (EC) displays with electronically regulating the transmittance of solar radiation offer the opportunity to increase the energy efficiency of the building and electronic products and improve the comfort and lifestyle of people. Despite the unique merit and vast application potential of EC technologies, long-awaited EC windows and related visual content displays have not been fully commercialized due to unsatisfactory production cost, durability, color, and complex fabrication processes. Here we develop a unique EC strategy and system based on the natural host and guest interactions to address the above issues. A completely reusable and sustainable EC device has been fabricated with potential advantages of extremely low cost, ideal user-/environment friendly property, and excellent optical modulation, which is benefited from the extracted biomass EC materials and reusable transparent electrodes involved in the system. The as-prepared EC window and nonemissive transparent display also show comprehensively excellent properties: high transmittance change (>85%), broad spectra modulation covering Ultraviolet (UV), Visible (Vis) to Infrared (IR) ranges, high durability (no attenuation under UV radiation for more than 1.5 mo), low open voltage (0.9 V), excellent reusability (>1,200 cycles) of the device's key components and reversibility (>4,000 cycles) with a large transmittance change, and pleasant multicolor. It is anticipated that unconventional exploration and design principles of dynamic host-guest interactions can provide unique insight into different energy-saving and sustainable optoelectronic applications.

Disulfidptosis-related genes of prognostic signature and immune infiltration features in hepatocellular carcinoma supported by bulk and single-cell RNA sequencing data.

Background: Disulfidptosis is a new type of cellular death triggered in response to disulfide stress and is strongly linked to the progression of malignancies. Hepatocellular carcinoma (HCC) is a very common malignancy. Some reports have suggested a link between disulfidptosis-related genes (DRGs) and cancer; however, further research needs to be conducted. Methods: In this study, HCC data from the Cancer Genome Atlas-Liver Hepatocellular Carcinoma and Gene Expression Omnibus data sets were collected and analyzed. A univariate Cox regression analysis, least absolute shrinkage and selection operator, and multivariate Cox regression analysis were conducted to identify the hub DRGs signature for prognosis. The HCC patients were allocated to high- and low-risk groups based on their disulfidptosis risk scores. The model was validated with a high degree of precision using both internal and external validation data sets. "ESTIMATE" and "CIBERSORT" packages were employed to assess the immunological landscapes and immune cell infiltration. The IMvigor210 cohort was chosen to validate the immunotherapy results. A drug sensitivity analysis was conducted to identify targeted medications. The expression of the hub DRGs in the HCC cells was confirmed using cytological techniques. Results: The bioinformatic analysis revealed that 16 genes showed differential expression. A prognostic model was developed based on four genes: RPN1, SLC2A1, SLC2A4, and SLC7A11. A notable difference in prognosis was observed between the two risk groups. Based on the results of the immune microenvironment, tumor mutation burden, immunotherapy, and drug screening analyses, the DRGs signature can be employed in HCC immunotherapy decision making. Further, the expression levels of the hub DRGs were significantly upregulated in the HCC cells. Conclusions: Our four-DRGs signature could be used to predict HCC prognosis. Further, this study showed that the hub DRGs could serve as biomarkers for immunotherapy prediction and could potentially guide targeted therapies.