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High-velocity, large-coupling acoustic mode is the eternal pursuit of microacoustic research. Surface mode on piezoelectric films supported by an acoustic Bragg reflector (ABR) stack is one possible solution for realizing such a goal. However, some acoustic modes exhibit lower couplings in experiments than theoretically predicted, especially when metal layers are used as high-impedance layers in the ABR. The mechanism of this performance deterioration is still unclear. In this work, the electric field distribution in a piezoelectric plate mounted to an ABR stack is analyzed by considering the inductive current effect in conductive ABR layers. The field distribution required by one mode is found to be distorted by the effect, which results in a reduction in the excitation efficiency for the mode. We propose the use of another acoustic mode with a concentrated electric field in the top layers. As analyzed in comparison, the impact of the inductive effect on the mode is negligible. On an optimized crystal cut of lithium niobate, the selected mode exhibits 22.64% coupling and an acoustic velocity of 6006 m/s. [ABSTRACT FROM AUTHOR]

The relation between hypertension (HTN) and cognition has been reported inclusive results, which may be affected by disease duration. Our study aimed to examine the influence of HTN duration on cognition and its underlying white matter (WM) changes including macrostructural WM hyperintensities (WMH) and microstructural WM integrity. A total of 1218 patients aged ≥55 years with neuropsychological assessment and a subgroup of 233 people with imaging data were recruited and divided into 3 groups (short duration: <5 years, medium duration: 5–20 years, long duration: >20 years). We found that greater HTN duration was preferentially related to worse executive function (EF), processing speed (PS), and more severe WMH, which became more significant during long duration stage. The reductions in WM integrity were evident at the early stage especially in long-range association fibers and then scattered through the whole brain. Increasing WMH and decreasing integrity of specific tracts consistently undermined EF. Furthermore, free water imaging method greatly enhanced the sensitivity in detecting HTN-related WM alterations. These findings supported that the neurological damaging effects of HTN is cumulative and neuroimaging markers of WM at macro- and microstructural level underlie the progressive effect of HTN on cognition. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma(HCC) is one of the most common tumors in the world. Human insulin-like growth factor 2(IGF2) mRNA binding protein 2(IGF2BP2) plays an important role in the progression of hepatocellular carcinoma. Additionally, long non-coding RNA(lncRNA) has been confirmed as a key regulator of hepatocellular carcinoma occurrence. However, the function of TRPC7-AS1 has not been verified in hepatocellular carcinoma. The research results revealed that high IGF2BP2 expression was associated with a decreased survival rate in patients with hepatocellular carcinoma. Furthermore, IGF2BP2 knockdown inhibited and IGF2BP2 overexpression promoted the cell proliferation and invasion of hepatocellular carcinoma cells. The research illuminated that IGF2BP2 regulated the expression of TRPC7-AS1, and a correlation was observed between IGF2BP2 and TRPC7-AS1 expression. TRPC7-AS1 silencing repressed and its overexpression promoted the progression of hepatocellular carcinoma. After silencing or overexpressing TRPC7-AS1, the expression of the high-mobility group AT-hook 2 (HMGA2) gene decreased or increased, respectively. IGF2BP2 enhanced the expression of TRPC7-AS1 and thus affected the expression of HMGA2, thereby promoting hepatocellular carcinoma progression. Note: This picture was drawed through the website. https://www.figdraw.com/#/ [Display omitted] • IGF2BP2 promotes the progression of hepatocellular carcinoma and has a great prognostic value in hepatocellular carcinoma. • IGF2BP2 regulates the expression of lncRNA TRPC7-AS1 in hepatocellular carcinoma. • LncRNA TRPC7-AS1 could be considered as an oncogene in hepatocellular carcinoma. • HMGA2 is a promotive factor in hepatocellular carcinoma progression. • IGF2BP2-lncRNA TRPC7-AS1 and HMGA2 axis promotes hepatocellular carcinoma cell proliferation and invasion. [ABSTRACT FROM AUTHOR]

[Display omitted] • BP-PEG could promote the accumulation and metabolism of P-Tau in the liver and kidneys. • BP-PEG could improve the symptoms of AD. • BP-PEG appear to be a safe and effective strategy for the peripheral clearance of P-Tau associated with AD. The onset of Alzheimer's disease (AD) is closely related to the accumulation of phosphorylated Tau proteins (P-Tau). However, due to the hindrance posed by the blood–brain barrier (BBB), current therapies targeting brain-derived P-Tau are largely ineffective. Interestingly, the clearance of peripheral P-Tau can eliminate P-Tau from the brain, enabling AD treatment and overcoming the challenges created by the BBB. Here, we prepared polyethylene glycol (PEG)-modified black phosphorus nanosheets (BP-PEG), which showed extended systemic circulation and acted as efficient "garbage trucks" for the removal of peripheral P-Tau. BP-PEG exhibited an exceptional capacity to bind to P-Tau in vitro. Further, in vivo biodistribution analysis demonstrated that BP-PEG accumulated in the liver and kidneys, which are the same organs that metabolize P-Tau. In vivo studies revealed that in okadaic acid (OA)-induced mouse models of AD, BP-PEG significantly reduced the levels of P-Tau in both the peripheral blood and the brain. Moreover, by promoting the clearance of peripheral P-Tau, BP-PEG improved several health indicators in mice, including cognitive function, glucose metabolism in the brain, inflammatory markers in the plasma and hippocampus, oxidative stress, and mitochondrial and myelin morphology. In conclusion, this study provides a new strategy for AD treatment, demonstrating the therapeutic value of removing P-Tau from the peripheral blood, and it also represents a novel attempt for the application of BP-PEG in AD therapy. [ABSTRACT FROM AUTHOR]

Senile osteoporosis—alternatively labeled as skeletal aging—encompasses age-induced bone deterioration and loss of bone microarchitecture. Recent studies have indicated a potential association between senile osteoporosis and chronic systemic inflammation, and pyroptosis in bone marrow-derived mesenchymal stem cells is speculated to contribute to bone loss and osteoporosis. Therefore, targeting pyroptosis in stem cells may be a potential therapeutic strategy for treating osteoporosis. Initially, we conducted bioinformatics analysis to screen the GEO databases to identify the key gene associated with pyroptosis in senile osteoporosis. Next, we analyzed the relationship between altered proteins and clinical data. In vitro experiments were then performed to explore whether the downregulation of PKM2 expression could inhibit pyroptosis. Additionally, an aging-related mouse model of osteoporosis was established to validate the efficacy of a PKM2 inhibitor in alleviating osteoporosis progression. We identified PKM2 as a key gene implicated in pyroptosis in senile osteoporosis patients through bioinformatics analysis. Further analyses of bone marrow and stem cells demonstrated significant PKM2 overexpression in senile osteoporosis patients. Silencing PKM2 expression inhibited pyroptosis in senile stem cells, of which the osteogenesis potential and angiogenic function were also primarily promoted. Moreover, the results in vivo demonstrated that administering PKM2 inhibitors suppressed pyroptosis in senile osteoporosis mice and mitigated senile osteoporosis progression. Our study uncovered PKM2, a key pyroptosis marker of bone marrow mesenchymal stem cells in senile osteoporosis. Shikonin, a PKM2 inhibitor, was then identified as a potential drug candidate for the treatment of osteoporosis. [Display omitted] • Our study identified a key pyroptosis marker, PKM2 in BMSCs of senile osteoporosis patients for the first time, which could be a novel diagnosis biomarker for SOP. • PKM2 was screened by bioinformatics and verified in aged mice and stem cells leading to bone loss through cellular pyroptosis via NLRP3/Caspase-1/GSDMD signaling pathway. • Shikonin, a potent PKM2 inhibitor, was identified for alleviating senile osteoporosis, which could provide a new direction for the prevention and treatment of other bone diseases. [ABSTRACT FROM AUTHOR]

Due to resistance and BCR-ABLT315I-mutated, CML remains a clinical challenge. It needs new potential therapeutic targets to overcome CML resistance related to BCR-ABL. Our research revealed that the deubiquitinating enzyme USP28 was highly expressed in BCR-ABL-dependent CML patients. Similarly, a high expression of USP28 was found in the K562 cell line, particularly in the imatinib-resistant strains. Notably, USP28 directly interacted with BCR-ABL. Furthermore, when BCR-ABL and its mutant BCR-ABLT315I were overexpressed in K562-IMR, they promoted the expression of IFITM3. However, when small molecule inhibitors targeting USP28 and small molecule degraders targeting BCR-ABL were combined, they significantly inhibited the expression of IFITM3. The experiments conducted on tumor-bearing animals revealed that co-treated mice showed a significant reduction in tumor size, effectively inhibiting the progression of CML tumors. In summary, USP28 promoted the proliferation and invasion of tumor cells in BCR-ABL-dependent CML by enhancing the expression of IFITM3. Moreover, imatinib resistance might be triggered by the activation of the USP28-BCR-ABL-IFITM3 pathway. Thus, the combined inhibition of USP28 and BCR-ABL could be a promising approach to overcome CML resistance dependent on BCR-ABL. [Display omitted] • DMP 11 is an innovatively synthesized protac compound targeting the degradation of the BCR-ABLfusion protein. • USP28 was correlated with the imatinib resistance in BCR-ABL-dependent CML. • Imatinib resistance may be triggered by the activation of the USP28-BCR-ABL-IFITM3 pathway. • Combined inhibition of USP28 and BCR-ABL may provide new potential therapeutic strategies to overcome CML resistance dependent on BCR-ABL. [ABSTRACT FROM AUTHOR]

• A novel gated graph neural network is proposed for water quality prediction. • Masking greatly enhances prediction accuracy, addressing sensor data limitation. • The model exhibits robust node-level prediction, enabling network soft sensing. • Sensor location plays a bigger role than quantity in improving prediction accuracy. Ensuring the safety and reliability of drinking water supply requires accurate prediction of water quality in water distribution networks (WDNs). However, existing hydraulic model-based approaches for system state prediction face challenges in model calibration with limited sensor data and intensive computing requirements, while current machine learning models are lack of capacity to predict the system states at sites that are not monitored or included in model training. To address these gaps, this study proposes a novel gated graph neural network (GGNN) model for real-time water quality prediction in WDNs. The GGNN model integrates hydraulic flow directions and water quality data to represent the topology and system dynamics, and employs a masking operation for training to enhance prediction accuracy. Evaluation results from a real-world WDN demonstrate that the GGNN model is capable to achieve accurate water quality prediction across the entire WDN. Despite being trained with water quality data from a limited number of sensor sites, the model can achieve high predictive accuracies (Mean Absolute Error = 0.07 mg L−1 and Mean Absolute Percentage Error = 10.0 %) across the entire network including those unmonitored sites. Furthermore, water quality-based sensor placement significantly improves predictive accuracy, emphasizing the importance of careful sensor location selection. This research advances water quality prediction in WDNs by offering a practical and effective machine learning solution to address challenges related to limited sensor data and network complexity. This study provides a first step towards developing machine learning models to replace hydraulic models in WDN modelling. [Display omitted] [ABSTRACT FROM AUTHOR]

Contamination events in water distribution networks (WDN) pose significant threats to water supply and public health. Rapid and accurate contamination source identification (CSI) can facilitate the development of remedial measures to reduce impacts. Though many machine learning (ML) methods have been proposed for fast detection, there is a critical need for approaches capturing complex spatial dynamics in WDNs to enhance prediction accuracy. This study proposes a gated graph neural network (GGNN) for CSI in the WDN, incorporating both spatiotemporal water quality data and flow directionality between network nodes. Evaluated across various contamination scenarios, the GGNN demonstrates high prediction accuracy even with limited sensor coverage. Notably, directional connections significantly enhance the GGNN CSI accuracy, underscoring the importance of network topology and flow dynamics in ML-based WDN CSI approaches. Specifically, the method achieves a 92.27% accuracy in narrowing the contamination source to 5 points using just 2 h of sensor data. The GGNN showcases resilience under model and measurement uncertainties, reaffirming its potential for real-time implementation in practice. Moreover, our findings highlight the impact of sensor sampling frequency and measurement accuracy on CSI accuracy, offering practical insights for ML methods in water network applications. • A gated graph neural network is proposed for contamination source identification. • The new model utilizes network topology and flow directions for enhanced performance. • Improved sensor sampling frequency and measurement accuracy boost model performance. • Model exhibits resilience to demand and measurement uncertainties. [ABSTRACT FROM AUTHOR]

Accumulating evidence indicates that exosomes help to regulate bone homeostasis. The roles of bone-derived exosomes have been well-described; however, recent studies have shown that some non-bone-derived exosomes have better bone targeting ability than bone-derived exosomes and that their performance as a drug delivery vehicle for regulating bone homeostasis may be better than that of bone-derived exosomes, and the sources of non-bone-derived exosomes are more extensive and can thus be better for clinical needs. Here, we sort non-bone-derived exosomes and describe their composition and biogenesis. Their roles and specific mechanisms in bone homeostasis and bone-related diseases are also discussed. Furthermore, we reveal obstacles to current research and future challenges in the practical application of exosomes, and we provide potential strategies for more effective application of exosomes for the regulation of bone homeostasis and the treatment of bone-related diseases. 67yBviMJcTRjcZnyRK6kR4 Video Abstract [ABSTRACT FROM AUTHOR]

To scavenge energy from imperceptible vibrations, this paper investigates the broadband response and output performance of a microvibrational piezoelectric energy harvesting system with mechanical stopper. The energy harvesting system comprises a cantilever beam made of piezoelectric material, which is affixed with a coil at its unbound end and a mechanical stopper. The coil is placed in a magnetic field to provide an ultra‐low level excitation. The electromechanical model is derived according to force integration method (FIM) and Hertz's contact theory, and numerical simulations are undertaken to evaluate the influence of the excitation level, and the gap on the performance. For the linear counterpart without stopper, experimental results indicate the system generates a peak power of 24.12 μW with matched resistance under excitation with a level of 0.003 N and a frequency of 200.3 Hz. When a polydimethylsiloxane (PDMS) stopper is introduced, the vibration of the piezoelectric beam exhibits an obvious nonlinearity with an amplitude of micron scale. Increasing the excitation level and decreasing the gap could efficiently broaden the response bandwidth. Experimental results demonstrate that a copper stopper with larger elastic modulus results in a wider response frequency range, and the half‐power bandwidth could reach 37.1 Hz under excitation with a level of 0.003 N. [ABSTRACT FROM AUTHOR]

• A rolling magnetic spring energy harvester is proposed for handshaking. • The influence of the coil's position on output performance is investigated. • Excitation with a level of 0.3 g witnesses a half-power bandwidth of 1.61 Hz. • Maximum average power of 2.22 mW is achieved under handshaking excitation. • Handshaking excitation in 5 s could enable a watch to operate for 1100 s. Aiming at the random and low-frequency characteristics of human motion, a hand-held rolling magnetic-spring energy harvester is proposed to scavenge energy from handshaking. The harvester applies the rolling movement of a magnetically suspended magnet and possesses the merit of low damping. The dynamic model is established and the open-circuit voltages are predicted by combining Faraday's law of electromagnetic induction and finite element analysis. By calculating magnetic flux through coils, the effect of the coil's position on energy harvesting efficiency is studied through numerical and experimental approaches. Experimental results under harmonic excitations indicate that the coil positioned directly below the stable equilibrium position of the moving magnet has the best output capability, and a maximum open-circuit voltage of 1.33 V and a half-power bandwidth of 1.61 Hz is achieved at 0.3 g. Under handshaking excitation, an instantaneous peak power of 20.15 mW is achieved, along with a maximum average power of 2.22 mW. The corresponding volume and mass power densities are respectively 26.04 μW/cm3 and 23.28 μW/g. Furthermore, handshaking excitation in 5 s to charge a capacitor of 470 μF could enable the watch, time display, timer, and hygrothermograph to operate for 1100 s, 513 s, 86 s, and 35 s respectively, demonstrating the brilliant application foreground of the proposed harvester. [ABSTRACT FROM AUTHOR]

In this study, we employed the principle of Relative Mode Transfer Method (RMTM) to establish a model for a single pendulum subjected to sudden changes in its length. An experimental platform for image processing was constructed to accurately track the position of a moving ball, enabling experimental verification of the pendulum's motion under specific operating conditions. The experimental data demonstrated excellent agreement with simulated numerical results, validating the effectiveness of the proposed methodology. Furthermore, we performed simulations of a double obstacle pendulum system, investigating the effects of different parameters, including obstacle pin positions, quantities, and initial release angles, on the pendulum's motion through numerical simulations. This research provides novel insights into addressing the challenges associated with abrupt and continuous changes in pendulum length. [ABSTRACT FROM AUTHOR]

Carbonate rock chemical weathering carbon sinks reduce the rate of increase of the atmospheric CO2 concentration and global warming. However, uncertainty still exists in the estimation results of carbonate rock chemical weathering carbon sink fluxes (CCSF), and the contributions of climate change and ecological restoration to the CCSF are not clear. To this end, we compiled published site data on ion concentrations in different watersheds in China and used a classical thermodynamic dissolution model to reassess the potential and spatial and temporal patterns of the CCSF in China from 1991 to 2020. We quantified the contributions of temperature (MAT), precipitation (MAP), evapotranspiration (ET), soil water (SM), and the normalized difference vegetation index (NDVI) to the CCSF. The results revealed that (1) China's CCSF was 22.76 t CO2 km−2 yr−1, which was higher than the global average (15.771CO2 km−2 yr−1). The total carbonate rock chemical weathering carbon sink (CCS) was 4772.67×104 t CO2, contributing 14.91% of the global CCS through a carbonate rock area of 252.98×104 km−2. (2) China's CCSF decreased gradually from southeast to northwest, with values of 33.14, 12.93, and 7.27 t CO2 km−2 yr−1 in the southern karst, Qinghai-Tibetan karst, and northern karst regions, respectively. (3) The overall CCSF in China exhibited an increasing trend from 1991 to 2020, with a rate of increase of 0.16 t CO2 km−2 yr−1. (4) The contributions of the MAP, MAT, ET, SM, and NDVI to the CCSF were 63.3%, 3.02%, 27.5%, 3.1%, and 3.05%, respectively. Among them, the increase in precipitation was the main contributor to the increase in the CCSF in China over the last 30 years, while the enhancement of ET offset part of the positive contribution of the increase in precipitation to the CCSF. In conclusion, the results of this study provide a systematic quantification of the magnitude, the patterns, and the influencing factors of CCS over a long time series in China. The results are of great significance and provide a reference for the diagnosis and gap analysis of the national and global carbon neutrality capacities. [ABSTRACT FROM AUTHOR]

• A novel automated approach was proposed for localizing seizure onset zone (SOZ) by cortico-cortical evoked potentials (CCEPs). • Cortical hyperexcitability at the stim-SOZ/rec-SOZ sites was increased in patients with hippocampus sclerosis compared to those with focal cortical dysplasia IIa. • The patients with complex partial seizures have more distinctive characteristics of CCEP than those with generalized tonic-clonic seizures in areas with different epileptogenicity. We aimed to develop a new approach for identifying the localization of the seizure onset zone (SOZ) based on corticocortical evoked potentials (CCEPs) and to compare the connectivity patterns in patients with different clinical phenotypes. Fifty patients who underwent stereoelectroencephalography and CCEP procedures were included. Logistic regression was used in the model, and six CCEP metrics were input as features: root mean square of the first peak (N1RMS) and second peak (N2RMS), peak latency, onset latency, width duration, and area. The area under the curve (AUC) for localizing the SOZ ranged from 0.88 to 0.93. The N1RMS values in the hippocampus sclerosis (HS) group were greater than that of the focal cortical dysplasia (FCD) IIa group (p < 0.001), independent of the distance between the recorded and stimulated sites. The sensitivity of localization was higher in the seizure-free group than in the non-seizure-free group (p = 0.036). This new method can be used to predict the SOZ localization in various focal epilepsy phenotypes. This study proposed a machine-learning approach for localizing the SOZ. Moreover, we examined how clinical phenotypes impact large-scale abnormality of the epileptogenic networks. [ABSTRACT FROM AUTHOR]

• A magnetic rolling pendulum bistable harvester is proposed for handshaking. • Complex dynamic behaviors and multiple solutions of the system are emphasized. • Bandwidth for high-energy orbit oscillation is 4.84 Hz under excitation of 0.5 g. • Matched impedance sees an average power of 4.21 mW under handshaking excitation. • Handshaking vibration in 13 s to charge a capacitor powers a watch for 44 min. Converting the kinetic energy of human movement into electricity provides a solution for the power supply of portable electronics for communication, medical treatment, positioning, search-and-rescue, etc. Due to the characteristics of high sensitivity and snap-through, a magnetic rolling pendulum bistable energy harvester (MRP-BEH) based on magnetic-spring mechanism is proposed for scavenging energy from handshaking vibration. The harvester possessing the advantage of small damping exploits the rolling oscillation of a suspended magnet. By establishing the electromechanical model, numerical outcomes of the MRP-BEHs with different potential well depths are investigated through the response under constant and sweep frequency excitations. Particularly, the complex dynamic behaviors are characterized by basins of attraction and bifurcation diagrams. A prototype is fabricated, and experiments are undertaken under harmonic and handshaking excitations. Experimental results are consistent with numerical simulations, and excitation of 0.5 g witnesses a broadband frequency range from 5.18 Hz to 10.02 Hz for the harvester with proper system parameters. Regarding the excitation of handshaking, an instantaneous maximum power of 21.9 mW and an average power of 4.21 mW is achieved with matched load resistance. By boosting the output voltage with a transformer, the charging and discharging experiments of capacitors for powering various electronics demonstrate the broad application prospects of the harvester. This research, in a nutshell, broadens the methodology for achieving bistable oscillation and introduces a fresh perspective for designing high-efficiency energy harvesters attuned to human motion. [ABSTRACT FROM AUTHOR]

• A novel dynamic unitary PV array reconfiguration method is proposed. • IPDO achieves the highest power over other eight comparison algorithms. • Four metrics are used to quantitatively assess various algorithms. • HIL experiments effectively validate the implementation feasibility of IPDO. • A new switch matrix is designed to reduce the switch number. This work designs an advanced dynamic unitary PV array reconfiguration scheme based on a novel improved prairie dog optimization (IPDO) to solve the power loss issue due to partial shading of PV arrays. This method takes the PV cell as the smallest entity of reconfiguration, and is suitable for large-scale PV arrays. To avoid invalid and redundant relocation of PV modules, an innovative self-rectify strategy is employed and embedded in the reconfiguration algorithm, which can reduce invalid actions of switching matrix by up to 80 %. Comparative simulation tests among nine algorithms (IPDO, genetic algorithm, particle swarm optimization, simulated annealing, four-square sudoku, arithmetic sequence pattern, modified harris hawks optimizer, artificial ecosystem-based optimization, Runge Kutta optimizer) under eight typical shading types verify the superiority of IPDO from four metrics, i.e., power loss, power enhancement, fill factor and execution ratio. Particularly, IPDO reduces power loss by 7.33 % to 30.63 %, enhances the harvested power by 6.1 % to 31.59 %, enhances fill factor (FF) by 0.579 to 0.773, and enhances execution ratio (ER) by 60.37 % to 92.67 % for asymmetric (20 × 30) PV array. For symmetric (30 × 30) PV array, IPDO reduces power loss by 9.01 % to 27.86 %, enhances the harvested power by 8.33 % to 43.69 %, enhances FF by 0.602 to 0.759, and enhances ER by 72.14 % to 90.99 %. Moreover, a new switching matrix with double-pole multi-throw switches is designed for the required switches number reduction. Lastly, hardware-in-the-loop (HIL) experiments based on RTLAB are carried out which validate the implementation feasibility of the proposed approach. [ABSTRACT FROM AUTHOR]

Immune-checkpoint blockade (ICB) therapies have been widely used in clinical treatment of cancer patients, but only 20–30% of patients benefit from immunotherapy. Therefore, it is important to decipher the molecular mechanism of resistance to ICB and develop new combined treatment strategies. PD-L1 up-regulation in tumor cells contributes to the occurrence of immune escape. Increasing evidence shows that its transcription level is affected by multiple factors, which limits the objective response rate of ICB. Fibroblast growth factor 19 (FGF19), a member of the fibroblast growth factor family, is widely involved in the malignant progression of many tumors by binding to fibroblast growth factor receptor 4 (FGFR4). In this study, we confirmed that FGF19 acts as a driver gene in hepatocellular carcinoma (HCC) progression by binding to FGFR4. The up-regulation of FGF19 and FGFR4 in HCC is associated with poor prognosis. We found that FGF19/FGFR4 promoted the proliferation and invasion of HCC cells by driving IGF2BP1 to promote PD-L1 expression. Knockdown of FGFR4 significantly reduced the expression of IGF2BP1/PD-L1 and inhibited the proliferation and invasion of HCC cells. These biological effects are achieved by inhibiting the PI3K/AKT pathway. The combination of FGFR4 knockdown and anti-PD-1 antibody greatly suppressed tumor growth and enhanced the sensitivity of immunotherapy, highlighting the clinical significance of FGF19/FGFR4 activation in immunotherapy. [Display omitted] • FGFR4 is upregulated and indicates poor prognosis in HCC patients. • FGF19/FGFR4 promotes IGF2BP1 expression and enhances PD-L1 transcription facilitation HCC cells survival and immune escape. • Anti-PD-1 combined with FGFR4 inhibition improves the sensitivity of HCC immunotherapy. [ABSTRACT FROM AUTHOR]