Glutamate dehydrogenase1 supports HIF-1α stability to promote colorectal tumorigenesis under hypoxia.

Tumor cells surviving hypoxic stress acquire the ability to drive cancer progression. To explore the contribution of dehydrogenases to the low oxygen concentration response, we used siRNAs targeting 163 dehydrogenase-coding genes and discovered that glutamate dehydrogenase 1 (GDH1) plays a critical role in regulating colorectal cancer (CRC) cell survival under hypoxia. We observed that GDH1 deficiency had an inhibitory effect on CRC occurrence and impaired hypoxia-inducible factor 1-alpha (HIF-1α) stability even under hypoxia. Mechanistically, hypoxia triggered p300 recruitment to GDH1, promoting its acetylation at K503 and K527. GDH1 acetylation at K527 induced the formation of a GDH1 complex with EGLN1/HIF-1α; in contrast, GDH1 acetylation at K503 reinforced its affinity for α-ketoglutarate (αKG), and glutamate production. In line with this view, αKG is a product of GDH1 under normoxia, but hypoxia stimulation reversed GDH1 enzyme activity and αKG consumption by the EGLN1/HIF-1α complex, increasing HIF-1α stability and promoting CRC progression. Clinically, hypoxia-modulated GDH1 AcK503/527 can be used as a biomarker of CRC progression and is a potential target for CRC treatment.

Cytosolic GDH1 degradation restricts protein synthesis to sustain tumor cell survival following amino acid deprivation.

The mTORC1 pathway plays key roles in regulating various biological processes, including sensing amino acid deprivation and driving expression of ribosomal protein (RP)-coding genes. In this study, we observed that depletion of glutamate dehydrogenase 1 (GDH1), an enzyme that converts glutamate to α-ketoglutarate (αKG), confers resistance to amino acid deprivation on kidney renal clear cell carcinoma (KIRC) cells. Mechanistically, under conditions of adequate nutrition, GDH1 maintains RP gene expression in a manner dependent on its enzymatic activity. Following amino acid deprivation or mTORC1 inhibition, GDH1 translocates from mitochondria to the cytoplasm, where it becomes ubiquitinated and degraded via the E3 ligase RNF213. GDH1 degradation reduces intracellular αKG levels by more than half and decreases the activity of αKG-dependent lysine demethylases (KDMs). Reduced KDM activity in turn leads to increased histone H3 lysine 9 and 27 methylation, further suppressing RP gene expression and preserving nutrition to support cell survival. In summary, our study exemplifies an economical and efficient strategy of solid tumor cells for coping with amino acid deficiency, which might in the future be targeted to block renal carcinoma progression.

Non-Covalent Interaction Enhancement on Active/Interfacial Layers via Two-Dimensional Vermiculite Doping for Efficient Organic Solar Cells.

Interface modification plays an important role in improving the power conversion efficiency (PCE) of organic solar cells (OSCs). However, the low non-covalent interaction between the cathode interface layer (CIL) and nonfullerene acceptor (NFA) directly affects the charge collection of OSCs. Here, the non-covalent interaction between the CIL and NFA is enhanced by introducing the 2D vermiculite (VML) in the poly(9,9-bis(3'-(N,N-dimethyl)-Nethylammonium-propyl-2,7-fluorene)-alt-2,7-(9,9-dioctylfluorene)) dibromide (PFN-Br) interface layer to form an efficient electron transport channel. As a result, the electron extraction efficiency from the active layer to the CIL is increased, and the PCE of OSCs based on PBDB-T:ITIC is boosted from 10.87% to 12.89%. In addition, the strategy of CIL doping VML is proven to be universal in different CIL materials, for which the PCE is boosted from 10.21% to 11.57% for OSCs based on PDINN and from 9.82% to 11.27% for OSCs based on PNDIT-F3N. The results provide a viable option for designing efficient CIL for high-performance non-fullerene OSCs, which may promote the commercialization of OSCs.

Recognition of Water-Induced Double-Edged Sword Effects in Photocatalytic Selective Oxidation of Toluene on Titanium Dioxide Clusters with Density Functional Theory Calculations.

Recently, water promotion effects in the selective oxidation of benzyl alcohol to benzaldehyde have been experimentally recognized and identified. However, the effects of water on the photocatalytic selective oxidation of toluene into benzaldehyde remain elusive. In this work, the Ti3O9H6 clusters in different solvents (water and toluene solvent) are used to study the water-induced effects in photocatalytic oxidation reactions in kinetics and thermodynamics using density functional theory (DFT) calculations. In addition, the influences of the OH groups on catalysts (Ti-OH bonds) from photocatalytic water splitting are also considered. The results clearly demonstrate the water-induced double-edged sword effects in the photocatalytic selective oxidation of toluene. We expect that our work can not only shed light on the mechanisms of photocatalytic selective oxidation of toluene into benzaldehyde and other activation reactions of sp3 C-H bonds but also design and modulate highly efficient photocatalysts.

Lesions in White Matter in Wilson's Disease and Correlation with Clinical Characteristics.

BACKGROUND: Neuroimaging studies in Wilson's disease (WD) have identified various alterations in white matter (WM) microstructural organization. However, it remains unclear whether these alterations are localized to specific regions of fiber tracts, and what diagnostic value they might have. The purpose of this study is to explore the spatial profile of WM abnormalities along defined fiber tracts in WD and its clinical relevance. METHODS: Ninety-nine patients with WD (62 men and 37 women) and 91 age- and sex-matched controls (59 men and 32 women) were recruited to take part in experiments of diffusion-weighted imaging with 64 gradient vectors. The data were calculated by FMRIB Software Library (FSL) software and Automated Fiber Quantification (AFQ) software. After registration, patient groups and normal groups were compared by Mann-Whitney U test analysis. RESULTS: Compared with the controls, the patients with WD showed widespread fractional anisotropy reduction and mean diffusivity, radial diffusivity elevation of identified fiber tracts. Significant correlations between diffusion tensor imaging (DTI) parameters and the neurological Unified Wilson's Disease Rating Scale (UWDRS-N), serum ceruloplasmin, and 24-h urinary copper excretion were found. CONCLUSIONS: The present study has provided evidence that the metrics of DTI could be utilized as a potential biomarker of neuropathological symptoms in WD. Damage to the microstructure of callosum forceps and corticospinal tract may be involved in the pathophysiological process of neurological symptoms in WD patients, such as gait and balance disturbances, involuntary movements, dysphagia, and autonomic dysfunction.

Large-scale networks changes in Wilson's disease associated with neuropsychiatric impairments: a resting-state functional magnetic resonance imaging study.

BACKGROUND: In Wilson's disease (WD) patients, network connections across the brain are disrupted, affecting multidomain function. However, the details of this neuropathophysiological mechanism remain unclear due to the rarity of WD. In this study, we aimed to investigate alterations in brain network connectivity at the whole-brain level (both intra- and inter-network) in WD patients through independent component analysis (ICA) and the relationship between alterations in these brain network functional connections (FCs) and clinical neuropsychiatric features to understand the underlying pathophysiological and central compensatory mechanisms. METHODS: Eighty-five patients with WD and age- and sex-matched 85 healthy control (HC) were recruited for resting-state functional magnetic resonance imaging (rs-fMRI) scanning. We extracted the resting-state networks (RSNs) using the ICA method, analyzed the changes of FC in these networks and the correlation between alterations in FCs and clinical neuropsychiatric features. RESULTS: Compared with HC, WD showed widespread lower connectivity within RSNs, involving default mode network (DMN), frontoparietal network (FPN), somatomotor network (SMN), dorsal attention network (DAN), especially in patients with abnormal UWDRS scores. Furthermore, the decreased FCs in the left medial prefrontal cortex (L_ MPFC), left anterior cingulate gyrus (L_ACC), precuneus (PCUN)within DMN were negatively correlated with the Unified Wilson's Disease Rating Scale-neurological characteristic examination (UWDRS-N), and the decreased FCs in the L_MPFC, PCUN within DMN were negatively correlated with the Unified Wilson's Disease Rating Scale-psychiatric symptoms examination (UWDRS-P). We additionally discovered that the patients with WD exhibited significantly stronger FC between the FPN and DMN, between the DAN and DMN, and between the FPN and DAN compared to HC. CONCLUSIONS: We have provided evidence that WD is a disease with widespread dysfunctional connectivity in resting networks in brain, leading to neurological features and psychiatric symptoms (e.g. higher-order cognitive control and motor control impairments). The alter intra- and inter-network in the brain may be the neural underpinnings for the neuropathological symptoms and the process of injury compensation in WD patients.

Engineering Giant Rabi Splitting via Strong Coupling between Localized and Propagating Plasmon Modes on Metal Surface Lattices: Observation of √N Scaling Rule.

We present a strong coupling system realized by coupling the localized surface plasmon mode in individual silver nanogrooves and propagating surface plasmon modes launched by periodic nanogroove arrays with varied periodicities on a continuous silver medium. When the propagating modes are in resonance with the localized mode, we observe a √N scaling of Rabi splitting energy, where N is the number of propagating modes coupled to the localized mode. Here, we confirm a giant Rabi splitting on the order of 450-660 meV (N = 2) in the visible spectral range, and the corresponding coupling strength is 160-235 meV. In some of the strong coupling cases studied by us, the coupling strength is about 10% of the mode energy, reaching the ultrastrong coupling regime.

High-performance photovoltaic application of the 2D all-inorganic Ruddlesden-Popper perovskite heterostructure Cs2PbI2Cl2/MAPbI3.

The three-dimensional (3D) organic-inorganic halide perovskite MAPbI3 has excellent light-harvesting properties but is unstable. However, the newly synthesized two-dimensional (2D) all-inorganic Ruddlesden-Popper (RP) perovskite Cs2PbI2Cl2 has superior stability but adverse photoelectric properties. Therefore, constructing a 2D Cs2PbI2Cl2/3D MAPbI3 heterostructure is expected to combine the superstability of the 2D material and the high efficiency of the 3D one. The photoelectric properties and charge transfer of 2D Cs2PbI2Cl2/3D MAPbI3 heterostructures are investigated using density functional theory, where MAPbI3 has two kinds of contacting interfaces, i.e., MAI and PbI interfaces. The band gaps of 2D/MAI and 2D/PbI heterostructures are 1.52 eV and 1.40 eV, smaller than those of the free-standing materials (2D ∼ 2.50 eV, MAI ∼ 1.77 eV, and PbI ∼ 1.73 eV), which can broaden the light absorption spectrum. Moreover, the 2D/3D heterostructures are typical type-II heterostructures, which is beneficial to facilitate the separation of carriers for increasing the photoelectric conversion. Interestingly, due to the work function difference (2D ∼ 4.97 eV, MAI ∼ 3.57 eV, and PbI ∼ 5.49 eV), the charge transfer directions of the 2D/MAI and 2D/PbI heterostructures are completely opposite, which shows that interface engineering to impose a consistent interface termination is needed to obtain good performance for solar cells. These results demonstrate that constructing 2D Cs2PbI2Cl2 and 3D MAPbI3 heterostructures by interfacial engineering is a potential strategy to improve the performance of perovskite solar cells (PSCs).

Effects of doping on photocatalytic water splitting activities of PtS2/SnS2 van der Waals heterostructures.

Photocatalytic water splitting is a promising technology to solve serious energy and environmental problems. The PtS2 monolayer has been previously predicted to be a water splitting photocatalyst. But the high efficiency of carrier recombination in the monolayer results in poor photocatalytic performance. It is well known that the construction of van der Waals (vdW) heterojunctions can improve the photocatalytic performance of a monolayer. In this investigation, we constructed a PtS2/SnS2 vdW heterojunction and systematically investigated the influence of the doping position and doping ratio on its performance using density functional theory calculations. Interestingly, the band alignment transforms from Type-II to Type-I and from Type-I to Type-II when the S in SnS2 is replaced with Se in the PtS2/SnS2 vdW heterojunction and the S in PtS2 is replaced with Se in the PtS2/SnSe2 vdW heterojunction, respectively. More importantly, from the PtS2/SnS2 to PtSe2/SnSe2 vdW heterojunction, the decomposition of water also changes from semi-decomposed water to fully decomposed water. Furthermore, the results show that the direct Z-scheme photocatalytic mechanism exists in the PtSSe/SnSe2 vdW heterojunction by analysis of the migration paths of photoinduced electrons and holes. And compared with the PtS2/SnS2, the PtSSe/SnSe2 heterostructure exhibits better photocatalytic water splitting activities. These results can provide a direction that doping can improve the photocatalytic water splitting performance of heterojunction photocatalysts.

Enhanced photocatalytic activity of the direct Z-scheme black phosphorus/BiOX (X = Cl, Br, I) heterostructures.

Bismuth oxyhalides (BiOX), as a typical photocatalytic material, have attracted much attention due to their unique layered structure, non-toxicity and excellent stability. However, the photocatalytic performance of BiOX is limited by their weak light absorption ability and rapid recombination of photo-generated carriers. In the present work, first-principles calculations have been performed to comprehensively explore the structural, electronic and optical properties of black phosphorus (BP)/BiOX (X = Cl, Br, I) heterostructures, revealing the inherent reasons for their enhanced photocatalytic performance. By combining band structures and work function analysis, the migration paths of photo-generated electrons and holes are obtained, proving a direct Z-scheme photocatalytic mechanism in BP/BiOX heterostructures. Moreover, the BP/BiOX heterostructures have decent band edge positions, which are suitable for photocatalytic overall water splitting. Compared with single BiOX, the light absorption performance of BP/BiOX heterostructures is significantly improved, in which BP/BiOI exhibits the highest optical absorption coefficient among the BP/BiOX heterostructures. Meanwhile, the better carrier migration performance of the BP/BiOX heterostructures is attributed to the reduction in effective mass. The present work offers theoretical insight into the application of BP/BiOX heterostructures as prominent photocatalysts for water splitting.

Epithelial EZH2 serves as an epigenetic determinant in experimental colitis by inhibiting TNFα-mediated inflammation and apoptosis.

Epithelial barrier disruption is a major cause of inflammatory bowel disease (IBD); however, the mechanism through which epigenetic regulation modulates intestinal epithelial integrity remains largely undefined. Here we show that EZH2, the catalytic subunit of polycomb repressive complex (PRC2), is indispensable for maintaining epithelial cell barrier integrity and homeostasis under inflammatory conditions. In accordance with reduced EZH2 expression in patients, the inactivation of EZH2 in IECs sensitizes mice to DSS- and TNBS-induced experimental colitis. Conversely, EZH2 overexpression in the intestinal epithelium renders mice more resistant to colitis. Mechanistically, the genes encoding TRAF2/5 are held in a finely tuned bivalent status under inflammatory conditions. EZH2 deficiency potentiates the expression of these genes to enhance TNFα-induced NF-κB signaling, thereby leading to uncontrolled inflammation. More importantly, we show that EZH2 depletion compromises the protective role of NF-κB signaling in cell survival by directly up-regulating ITCH, a well-known E3 ligase that degrades the c-FLIP protein. Thus, our findings highlight an epigenetic mechanism by which EZH2 integrates the multifaceted effects of TNFα signaling to promote the inflammatory response and apoptosis in colitis.

Effects of puerarin on the pharmacokinetics of triptolide in rats.

Context: Puerarin and triptolide are sometimes used together for the treatment of disease in Chinese clinics; however, the drug-drug interaction between puerarin and triptolide is still unknown. Objective: This study investigates the effects of puerarin on the pharmacokinetics of triptolide in rats and clarifies its main mechanism. Materials and methods: The pharmacokinetic profiles of oral administration of triptolide (1 mg/kg) in Sprague-Dawley rats with (test group, n = 6) or without pretreatment (control group, n = 6) with puerarin (100 mg/kg/day for seven days) were investigated. The effects of puerarin on the transport and metabolic stability of triptolide were also investigated using Caco-2 cell transwell model and rat liver microsomes. Results: The results showed that puerarin could significantly increase the peak plasma concentration (from 187.25 ± 15.36 to 219.67 ± 21.52 ng/mL), and decrease its oral clearance (from 4.92 ± 0.35 to 62.46 ± 3.75 ± 0.19 L/h/kg). The Caco-2 cell transwell experiments indicated that puerarin could decrease the efflux ratio of triptolide from 2.70 to 1.33, and the intrinsic clearance rate of triptolide was decreased by the pretreatment with puerarin (38.8 ± 4.7 vs. 32.9 ± 6.5 µL/min/mg protein). Discussion and conclusions: Puerarin could significantly change the pharmacokinetic profiles of triptolide in rats, and it might exert these effects through increasing the absorption of triptolide by inhibiting the activity of P-gp, or through inhibiting the metabolism of triptolide in rat liver. The results also showed that the dose of triptolide should be decreased when these drugs were co-administered.

HIC1 loss promotes prostate cancer metastasis by triggering epithelial-mesenchymal transition.

Metastatic disease is the leading cause of death due to prostate cancer (PCa). Although the hypermethylated in cancer 1 (HIC1) gene has been observed to be epigenetically modified in PCa, its intrinsic role and mechanism in PCa metastasis still remain uncertain. Here, we show that hypermethylation of the HIC1 promoter markedly reduces its suppressive function in metastatic PCa tissues as compared with primary and adjacent normal prostate tissues, and is associated with poor patient survival. PCas in cancer-prone mice homozygous for a prostate-targeted Hic1 conditional knockout showed stronger metastatic behaviour than those in heterozygous mice, as a result of epithelial-mesenchymal transition (EMT). Moreover, impairment of HIC1 expression in PCa cells induced their migration and metastasis through EMT, by enhancing expression of Slug and CXCR4, both of which are critical to PCa metastasis; the CXCL12-CXCR4 axis promotes EMT by activating the extracellular signal-regulated kinase (ERK) 1/2 pathway. Taken together, our results suggest that evaluation of HIC1-CXCR4-Slug signalling may provide a potential predictor for PCa aggressiveness. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Population pharmacokinetics of arginine glutamate in healthy Chinese volunteers.

1. The present study developed population pharmacokinetic models of arginine and glutamate in healthy Chinese volunteers. Two nonlinear mixed-effect models were developed using NONMEM® software (ICON Development Solutions, Ellicott City, MD) to describe the pharmacokinetic properties and to assess the relevant parameters as well as the inter-individual variability. The potential covariates were screened using stepwise approach and the stability and predictive capability of the models were performed using bootstrap and visual predictive check. 2. The concentration time curves of arginine and glutamate were best described by a first-order elimination two-compartment model and a nonlinear elimination one-compartment model, respectively. The final parameter estimation of arginine for CL was 44.1 L/h. Q, V1 and V2 were 23 L/h, 20.3 L and 46 L, respectively. The final parameter estimation of glutamate for Vmax and Km were 18.8 mg/h and 77.2 mg/L, respectively. V for low dose and high dose was 23.1 L and 36.3 L, respectively. 3. For arginine, weight was significant covariate on the apparent distribution volume of peripheral compartment. The gain in weight remarkably increases V2. For glutamate, dose as a significant covariate on the apparent distribution volume was included, subjects received high dose (20 g) have remarkably higher V compared to subjects received low dose (10 g).

The availability, price and affordability of essential antibacterials in Hubei province, China.

BACKGROUND: China ranks first amongst the countries for the abuse of antibacterials. Essential antibacterials could help solve the problem. The aim of the work is to evaluate the availability, price and affordability of essential antibacterials in Hubei province, China. METHOD: The standardized methodology developed by the World Health Organization and Health Action International was used to collect data on the availability and prices of 16 antibacterials in 5 cities of Hubei province, China. RESULTS: First, in total, the median availability of originator brands and lowest-priced generics for the essential antibacterials was low, 3.0% (0.0, 18.2%) and 33.3% (0.0, 87.9%) for each, respectively. Second, the median price ratio of originator brands for the antibacterials was 20.30 (4.71, 35.80), while for generics, it was 0.49 (0.07, 1.18). Third, the affordability of originator brands for the antibacterials was 28.14 (21.70, 41.90) times the daily wages of an unskilled government worker, while for generics, the affordability was 0.35 (0.04, 6.11). Finally, we found that in Hubei province, lowest-priced generics for essential antibacterials with (fairly) high availability and relatively low price included Amoxicillin/Clavulanic Acid, Ceftazidime, Metronidazole, Gentamicin Sulfate and Ceftriaxone. CONCLUSION: The prices of lowest-priced generics for essential antibacterials in Hubei province were reasonable, and in tertiary hospitals the availability was the highest, while in secondary and primary hospitals, it was relatively lower. Originator brands were not only extremely expensive but also difficult to obtain. Measures should be taken to improve the availability of essential antibacterials and the affordability of originator brands.

Quantitative and Sensitive Detection of Chloramphenicol by Surface-Enhanced Raman Scattering.

We used surface-enhanced Raman scattering (SERS) for the quantitative and sensitive detection of chloramphenicol (CAP). Using 30 nm colloidal Au nanoparticles (NPs), a low detection limit for CAP of 10-8 M was obtained. The characteristic Raman peak of CAP centered at 1344 cm-1 was used for the rapid quantitative detection of CAP in three different types of CAP eye drops, and the accuracy of the measurement result was verified by high-performance liquid chromatography (HPLC). The experimental results reveal that the SERS technique based on colloidal Au NPs is accurate and sensitive, and can be used for the rapid detection of various antibiotics.

Abnormalities in subcortical function and their treatment response in Wilson's disease.

Extensive neuroimaging abnormalities in subcortical regions build the pathophysiological basis of Wilson's disease (WD). Yet, subcortical topographic organization fails to articulate, leaving a huge gap in understanding the neural mechanism of WD. Thus, how functional abnormalities of WD subcortical regions influence complex clinical symptoms and response to treatment remain unknown. Using resting-state functional MRI data from 232 participants (including 130 WD patients and 102 healthy controls), we applied a connectivity-based parcellation technique to develop a subcortical atlas for WD. The atlas was further used to investigate abnormalities in subcortical function (ASF) by exploring intrasubcortical functional connectivity (FC) and topographic organization of cortico-subcortical FC. We further used support vector machine (SVM) to integrate these functional abnormalities into the ASF score, which serves as a biomarker for characterizing individual subcortical dysfunction for WD. Finally, the baseline ASF score and one-year treatment data of the follow-up WD patients were used to assess treatment response. A group set of subcortical parcellations was evaluated, in which 26 bilateral regions well recapitulated the anatomical nuclei of the subcortical areas of WD. The results of cortico-subcortical FC and intrasubcortical FC reveal that dysfunction of the somatomotor networks-lenticular nucleus-thalamic pathways is involved in complex symptoms of WD. The ASF score was able to characterize disease progression and was significantly associated with treatment response of WD. Our findings provide a comprehensive elaboration of functional abnormalities of WD subcortical regions and reveal their association with clinical presentations, improving our understanding of the functional neural underpinnings in WD. Furthermore, abnormalities in subcortical function could serve as a potential biomarker for understanding the disease progression and evaluating treatment response of WD.

Decoding Wilson disease: a machine learning approach to predict neurological symptoms.

Objectives: Wilson disease (WD) is a rare autosomal recessive disorder caused by a mutation in the ATP7B gene. Neurological symptoms are one of the most common symptoms of WD. This study aims to construct a model that can predict the occurrence of neurological symptoms by combining clinical multidimensional indicators with machine learning methods. Methods: The study population consisted of WD patients who received treatment at the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from July 2021 to September 2023 and had a Leipzig score ≥ 4 points. Indicators such as general clinical information, imaging, blood and urine tests, and clinical scale measurements were collected from patients, and machine learning methods were employed to construct a prediction model for neurological symptoms. Additionally, the SHAP method was utilized to analyze clinical information to determine which indicators are associated with neurological symptoms. Results: In this study, 185 patients with WD (of whom 163 had neurological symptoms) were analyzed. It was found that using the eXtreme Gradient Boosting (XGB) to predict achieved good performance, with an MCC value of 0.556, ACC value of 0.929, AUROC value of 0.835, and AUPRC value of 0.975. Brainstem damage, blood creatinine (Cr), age, indirect bilirubin (IBIL), and ceruloplasmin (CP) were the top five important predictors. Meanwhile, the presence of brainstem damage and the higher the values of Cr, Age, and IBIL, the more likely neurological symptoms were to occur, while the lower the CP value, the more likely neurological symptoms were to occur. Conclusions: To sum up, the prediction model constructed using machine learning methods to predict WD cirrhosis has high accuracy. The most important indicators in the prediction model were brainstem damage, Cr, age, IBIL, and CP. It provides assistance for clinical decision-making.

Cost-effectiveness of nivolumab versus sorafenib as first-line treatment for advanced hepatocellular carcinoma.

BACKGROUND: Nivolumab improves overall survival (OS) and is associated with less adverse events (AE) compared with sorafenib in the first-line treatment of advanced hepatocellular carcinoma (HCC). But which approach is the most cost-effective remains uncertain. This study aimed to evaluate the cost-effectiveness of nivolumab vs sorafenib as first-line therapy for patients with advanced HCC from the perspective of Chinese healthcare system. METHODS: A partitioned survival mode was constructed to evaluate the health and economic outcomes of nivolumab vs sorafenib as first-line treatment for advanced HCC. The clinical data and outcomes were obtained from CheckMate 459 trial. Medical costs and utilities were collected from published sources. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. One-way and probabilistic sensitivity analyses were used to examine model uncertainty. Additional subgroup and scenario analyses were performed. RESULTS: Treatment with nivolumab yielded an additional 0.27 QALYs with an incremental cost of $65,579.19 compared with sorafenib, leading to an ICER of $236,765.93/QALY in China. One-way sensitivity analysis found the model outputs to be most affected for hazard ratio (HR) of OS and the cost of nivolumab. Probabilistic sensitivity analysis showed that the probability of nivolumab being cost-effective was 0% at the willingness-to-pay (WTP) threshold of $38,201.19/QALY. The scenario analyses indicated altering the time horizon of the model did not reverse the economic results. CONCLUSION: Nivolumab as first-line treatment could gain more health benefits for advanced HCC compared with sorafenib, but was estimated not to be cost-effective at the commonly adopted WTP threshold of China.