The endpoint carbon content in the converter is critical for the quality of steel products,and accurately predicting this parameter is an effective way to reduce alloy consumption and improve smelting efficiency.Howev...The endpoint carbon content in the converter is critical for the quality of steel products,and accurately predicting this parameter is an effective way to reduce alloy consumption and improve smelting efficiency.However,most scholars currently focus on modifying methods to enhance model accuracy,while overlooking the extent to which input parameters influence accuracy.To address this issue,in this study,a prediction model for the endpoint carbon content in the converter was developed using factor analysis(FA)and support vector machine(SVM)optimized by improved particle swarm optimization(IPSO).Analysis of the factors influencing the endpoint carbon content during the converter smelting process led to the identification of 21 input parameters.Subsequently,FA was used to reduce the dimensionality of the data and applied to the prediction model.The results demonstrate that the performance of the FA-IPSO-SVM model surpasses several existing methods,such as twin support vector regression and support vector machine.The model achieves hit rates of 89.59%,96.21%,and 98.74%within error ranges of±0.01%,±0.015%,and±0.02%,respectively.Finally,based on the prediction results obtained by sequentially removing input parameters,the parameters were classified into high influence(5%-7%),medium influence(2%-5%),and low influence(0-2%)categories according to their varying degrees of impact on prediction accuracy.This classi-fication provides a reference for selecting input parameters in future prediction models for endpoint carbon content.展开更多
We study the production of the X(6900)in the ultra-peripheral heavy ion collisions at the LHC energy region.The potential quantum numbers of X(6900)could be 0^(±+)and 2^(±+).We find that the transverse momen...We study the production of the X(6900)in the ultra-peripheral heavy ion collisions at the LHC energy region.The potential quantum numbers of X(6900)could be 0^(±+)and 2^(±+).We find that the transverse momentum and the polar angle distributions of X(6900)can be used to distinguish these four potential quantum numbers.These characteristic distributions originate from linearly polarized photons emitted by relativistic nuclei and can be measured by further LHC experiments.展开更多
Osteoarthritis(OA)is one of the most common degenerative joint diseases in the elderly,increasing in prevalence and posing a substantial socioeconomic challenge,while no disease-modifying treatments available.Better u...Osteoarthritis(OA)is one of the most common degenerative joint diseases in the elderly,increasing in prevalence and posing a substantial socioeconomic challenge,while no disease-modifying treatments available.Better understanding of the early molecular events will benefit the early-stage diagnosis and clinical therapy.Here,we observed the nucleus accumulation of ZBTB20,a member of ZBTB-protein family,in the chondrocytes of early-stage OA.Chondrocytes-specific depletion of Zbtb20 in adult mice attenuated DMM-induced OA progress,restored the balance of extracellular matrix anabolism and catabolism.The NF-κB signaling mediated disturbance of ECM maintenance by ZBTB20 requires its suppression of Pten and consequent PI3K-Akt signaling activation.Furthermore,the subcellular localization of ZBTB20 was modulated by the kinase LATS1.Independent approaches to modulating ZBTB20 via utilizing TRULI and DAPA can restore ECM homeostasis,improving the abnormal behavior and moderating cartilage degeneration.The compounds TRULI and DAPA modulating ZBTB20 may serve as anti-OA drugs.展开更多
Oral ulcers are a common ulcerative injury that occurs in the oral mucosa.When occurring,they can cause mucosal pain and affect eating and communication.The oral cavity,characterized by its moist environment and const...Oral ulcers are a common ulcerative injury that occurs in the oral mucosa.When occurring,they can cause mucosal pain and affect eating and communication.The oral cavity,characterized by its moist environment and constant movement of the lips and tongue,presents challenges for conventional drug delivery systems due to its suboptimal adhesion.Therefore,there is a need for the development of adhesive materials specifically designed for use within the oral cavity.In this research,a sticky coacervate incorporating tea polyphenols(TP)was formulated based on the adhesive properties observed in sandcastle worms.The coacervate is composed of Pluronic F68(F68)and TP,synthesized through the coacervation reaction.The F68-TP coacervates are attached to porcine skin easily.It also reduces bacterial viability and has the ability to clear reactive oxygen species.In animal ulcer models,these coacervates demonstrate anti-inflammatory effects and enhance collagen and muscle fiber synthesis.Overall,these adhesive coacervates with antioxidative and antibacterial properties hold potential as a therapeutic option for oral ulcers in the oral cavity.展开更多
A novel NiAlTa blade tip protective coating is designed and its oxidation,hot corrosion,and interdiffusion with DD5 single-crystal superalloys are investigated.NiAlTa coatings exhibit low oxidation rates.The dragging ...A novel NiAlTa blade tip protective coating is designed and its oxidation,hot corrosion,and interdiffusion with DD5 single-crystal superalloys are investigated.NiAlTa coatings exhibit low oxidation rates.The dragging effect of Ta on Al hinders the external diffusion of Al.Ta that accumulates at the Al_(2)O_(3)grain boundaries reduces the internal diffusion of O by combining or reacting with it.NaCl aggravates the hot corrosion through self ustaining cycles of chlorination/oxidation.β-NiAl phase fails first as a diffusion channel for the corrosive medium.Significant element interdiffusion occurs.An interdiffusion zone and a secondary reaction zone are formed.Interdiffusion changes the percentage of elements,causing a phase transition of the coating.The volume change caused by the phase transition induces bulging and cracking of the oxide film.Furthermore,the oxidation,hot corrosion,and interdiffusion mechanisms are discussed.展开更多
Electron-positron colliders operating in the GeV center-of-mass range,or tau-charm energy region,have been proved to enable competitive frontier research due to several unique features.With the progress of high-energy...Electron-positron colliders operating in the GeV center-of-mass range,or tau-charm energy region,have been proved to enable competitive frontier research due to several unique features.With the progress of high-energy physics in the last two decades,a new-generation Tau-Charm factory,called the Super Tau-Charm Facility(STCF),has been actively promoted by the particle physics community in China.STCF has the potential to address fundamental questions such as the essence of color confinement and the matter-antimatter asymmetry within the next decades.The main design goals of the STCF are a center-of-mass energy ranging from 2 to 7 GeV and a luminosity surpassing 5×10^(34)cm^(−2)s^(−1)that is optimized at a center-of-mass energy of 4 GeV,which is approximately 50 times that of the currently operating Tau-Charm factory-BEPCII.The STCF accelerator has two main parts:a double-ring collider with a crab-waist collision scheme and an injector that provides top-up injections for both electron and positron beams.As a typical third-generation electron-positron circular collider,the STCF accelerator faces many challenges in both accelerator physics and technology.In this paper,the conceptual design of the STCF accelerator complex is presented,including the ongoing efforts and plans for technological research and develop-ment,as well as the required infrastructure.The STCF project aims to secure support from the Chinese central government for its construction during the 15th Five-Year Plan(2026-2030).展开更多
Large-aperture optical components are of paramount importance in domains such as integrated circuits,photolithography,aerospace,and inertial confinement fusion.However,measuring their surface profiles relies predomina...Large-aperture optical components are of paramount importance in domains such as integrated circuits,photolithography,aerospace,and inertial confinement fusion.However,measuring their surface profiles relies predominantly on the phase-shifting approach,which involves collecting multiple interferograms and imposes stringent demands on environmental stability.These issues significantly hinder its ability to achieve real-time and dynamic high-precision measurements.Therefore,this study proposes a high-precision large-aperture single-frame interferometric surface profile measurement(LA-SFISPM)method based on deep learning and explores its capability to realize dynamic measurements with high accuracy.The interferogram is matched to the phase by training the data measured using the small aperture.The consistency of the surface features of the small and large apertures is enhanced via contrast learning and feature-distribution alignment.Hence,high-precision phase reconstruction of large-aperture optical components can be achieved without using a phase shifter.The experimental results show that for the tested mirror withΦ=820 mm,the surface profile obtained from LA-SFISPM is subtracted point-by-point from the ground truth,resulting in a maximum single-point error of 4.56 nm.Meanwhile,the peak-to-valley(PV)value is 0.0758λ,and the simple repeatability of root mean square(SR-RMS)value is 0.00025λ,which aligns well with the measured results obtained by ZYGO.In particular,a significant reduction in the measurement time(reduced by a factor of 48)is achieved compared with that of the traditional phase-shifting method.Our proposed method provides an efficient,rapid,and accurate method for obtaining the surface profiles of optical components with different diameters without employing a phase-shifting approach,which is highly desired in large-aperture interferometric measurement systems.展开更多
Thermosyphon loops are widely used in cooling systems.However,such distributed thermal management systems lack the ability to actively control the coolant flow in each parallel branch.An effective method for addressin...Thermosyphon loops are widely used in cooling systems.However,such distributed thermal management systems lack the ability to actively control the coolant flow in each parallel branch.An effective method for addressing this is to control the coolant flow in each branch using a solenoid valve.However,the existing valves do not satisfy the requirements for fast switching,low power,low pressure loss,and miniaturization.Therefore,in this study,a low-power-consumption miniature solenoid valve(LMSV)is proposed for use in thermal management systems.The key novelty is that the valve is designed with a suitably sized permanent magnet(PM)to allow the spool to continue working without consuming electrical energy.To achieve low flow resistance,a straight-through design is employed in the valve with the electromagnetic actuator located inside the valve shell.Multiphysical coupling analysis is performed to investigate its performance.The influence of the PM dimensions and current on the magnetic field distribution and electromagnetic force is studied.The effects of these key parameters on the flow field and pressure loss are also analyzed.Because the LMSV is sensitive to temperature,the switching time and energy consumption at different working temperatures are investigated.Experimental test platforms are constructed.A valve switching time of as short as 3 ms,pressure loss of 200 Pa at 0.92 L/min,and energy consumption of approximately 1.55 J during the opening and closing processes are achieved.The novel solenoid valve proposed in this study offers fast switching,low power consumption,low pressure loss,and miniaturization to meet the requirements of thermal management systems.展开更多
In the era of big data,personalised recommendation systems are essential for enhancing user engagement and driving business growth.However,traditional recommendation algorithms,such as collaborative filtering,face sig...In the era of big data,personalised recommendation systems are essential for enhancing user engagement and driving business growth.However,traditional recommendation algorithms,such as collaborative filtering,face significant challenges due to data sparsity,algorithm scalability,and the difficulty of adapting to dynamic user preferences.These limitations hinder the ability of systems to provide highly accurate and personalised recommendations.To address these challenges,this paper proposes a clustering-based recommendation method that integrates an enhanced Grasshopper Optimisation Algorithm(GOA),termed LCGOA,to improve the accuracy and efficiency of recommendation systems by optimising cluster centroids in a dynamic environment.By combining the K-means algorithm with the enhanced GOA,which incorporates a Lévy flight mechanism and multi-strategy co-evolution,our method overcomes the centroid sensitivity issue,a key limitation in traditional clustering techniques.Experimental results across multiple datasets show that the proposed LCGOA-based method significantly outperforms conventional recommendation algorithms in terms of recommendation accuracy,offering more relevant content to users and driving greater customer satisfaction and business growth.展开更多
The application of tumor antigen-based immunotherapy is hindered by the rarity of validated immunogenic peptides.In this study,we aimed to investigate the potential of circular RNAs(circRNAs)as a novel source of tumor...The application of tumor antigen-based immunotherapy is hindered by the rarity of validated immunogenic peptides.In this study,we aimed to investigate the potential of circular RNAs(circRNAs)as a novel source of tumor antigen peptides in hepatobiliary tumor organoids.Using RNA-sequencing(RNA-seq)with an algorithm-based score tool,3950 translated tumor-specific circRNAs were predicted to generate 18971 antigen peptides in 27 organoids.In view of the antigen landscape,11 amino acid length(mer)peptides and human leukocyte antigen(HLA)-A binding peptides harbored the highest immunogenicity-related scores.In three out of five analyzed organoids,13 predicted antigen peptides were directly confirmed as HLA-A,-B,and-C(HLA-ABC)binding peptides with mass spectrometry(MS)-based immunopeptidomics.CircRNA-derived tumor-specific peptides presented by the HLA-ABC molecules stimulated cluster of differentiation 8(CD8)T cells to exhibit increased CD107a interferonγ(IFNγ)co-expressions and IFNγsecretion in flow cytometry and enzyme-linked immunosorbent assay(ELISA).Cytotoxic T cell activity targeting the organoids,induced by the immunogenic circRNA-derived peptides,was verified in a killing assay.Notably,the antigen peptide YGFNEILKK from circTBC1D15 was not only recognized as an HLA-ABC-presented peptide of the organoids but also drastically reduced the tumor organoid survival rate.Our findings highlight a crucial subset for generating tumor antigens,which has implications for targeting tumor-specific circRNAs in cancers.展开更多
基金financially supported by the National Natural Science Foundation of China(No.52174297).
文摘The endpoint carbon content in the converter is critical for the quality of steel products,and accurately predicting this parameter is an effective way to reduce alloy consumption and improve smelting efficiency.However,most scholars currently focus on modifying methods to enhance model accuracy,while overlooking the extent to which input parameters influence accuracy.To address this issue,in this study,a prediction model for the endpoint carbon content in the converter was developed using factor analysis(FA)and support vector machine(SVM)optimized by improved particle swarm optimization(IPSO).Analysis of the factors influencing the endpoint carbon content during the converter smelting process led to the identification of 21 input parameters.Subsequently,FA was used to reduce the dimensionality of the data and applied to the prediction model.The results demonstrate that the performance of the FA-IPSO-SVM model surpasses several existing methods,such as twin support vector regression and support vector machine.The model achieves hit rates of 89.59%,96.21%,and 98.74%within error ranges of±0.01%,±0.015%,and±0.02%,respectively.Finally,based on the prediction results obtained by sequentially removing input parameters,the parameters were classified into high influence(5%-7%),medium influence(2%-5%),and low influence(0-2%)categories according to their varying degrees of impact on prediction accuracy.This classi-fication provides a reference for selecting input parameters in future prediction models for endpoint carbon content.
基金supported by the Guangdong Major Project of Basic and Applied Basic Research(Grant Nos.2020B0301030008 and 2023A1515010416)the National Natural Science Foundation of China(Grant Nos.12375073,12275091,12147128,and 12035007).
文摘We study the production of the X(6900)in the ultra-peripheral heavy ion collisions at the LHC energy region.The potential quantum numbers of X(6900)could be 0^(±+)and 2^(±+).We find that the transverse momentum and the polar angle distributions of X(6900)can be used to distinguish these four potential quantum numbers.These characteristic distributions originate from linearly polarized photons emitted by relativistic nuclei and can be measured by further LHC experiments.
基金supported by grants from the National Natural Science Foundation of China(82002351,82394442,82130070,82272442)funded by the Innovation Capability Support Program of Shaanxi Province(2024SF-LCZX-16)+2 种基金the Shaanxi Province Health Scientific Research Innovation Ability Promotion Plan(2024PT-12)the Independent Exploration and Innovation Project of Xi’an Jiaotong University(xzy012023121)the project of Xi’an Postdoctoral Innovation Base.
文摘Osteoarthritis(OA)is one of the most common degenerative joint diseases in the elderly,increasing in prevalence and posing a substantial socioeconomic challenge,while no disease-modifying treatments available.Better understanding of the early molecular events will benefit the early-stage diagnosis and clinical therapy.Here,we observed the nucleus accumulation of ZBTB20,a member of ZBTB-protein family,in the chondrocytes of early-stage OA.Chondrocytes-specific depletion of Zbtb20 in adult mice attenuated DMM-induced OA progress,restored the balance of extracellular matrix anabolism and catabolism.The NF-κB signaling mediated disturbance of ECM maintenance by ZBTB20 requires its suppression of Pten and consequent PI3K-Akt signaling activation.Furthermore,the subcellular localization of ZBTB20 was modulated by the kinase LATS1.Independent approaches to modulating ZBTB20 via utilizing TRULI and DAPA can restore ECM homeostasis,improving the abnormal behavior and moderating cartilage degeneration.The compounds TRULI and DAPA modulating ZBTB20 may serve as anti-OA drugs.
基金supported by the National Natural Science Foundation(No.32271468)Sichuan Science and Technology Program(No.2021JDTD0001)+2 种基金1·3·5 Project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYYC23005)the Fundamental Research Funds for the Central Universities(No.2022SCU12046)Innovation Research Project of Sichuan University(No.2022SCUH0046).
文摘Oral ulcers are a common ulcerative injury that occurs in the oral mucosa.When occurring,they can cause mucosal pain and affect eating and communication.The oral cavity,characterized by its moist environment and constant movement of the lips and tongue,presents challenges for conventional drug delivery systems due to its suboptimal adhesion.Therefore,there is a need for the development of adhesive materials specifically designed for use within the oral cavity.In this research,a sticky coacervate incorporating tea polyphenols(TP)was formulated based on the adhesive properties observed in sandcastle worms.The coacervate is composed of Pluronic F68(F68)and TP,synthesized through the coacervation reaction.The F68-TP coacervates are attached to porcine skin easily.It also reduces bacterial viability and has the ability to clear reactive oxygen species.In animal ulcer models,these coacervates demonstrate anti-inflammatory effects and enhance collagen and muscle fiber synthesis.Overall,these adhesive coacervates with antioxidative and antibacterial properties hold potential as a therapeutic option for oral ulcers in the oral cavity.
基金financially supported by the Strategic Priority Research Program of the Chinese Academy of Sciences,Grant(No.XDB 047010204)Liaoning Key Laboratory of Aero-engine Material Tribology for both financial and facility support
文摘A novel NiAlTa blade tip protective coating is designed and its oxidation,hot corrosion,and interdiffusion with DD5 single-crystal superalloys are investigated.NiAlTa coatings exhibit low oxidation rates.The dragging effect of Ta on Al hinders the external diffusion of Al.Ta that accumulates at the Al_(2)O_(3)grain boundaries reduces the internal diffusion of O by combining or reacting with it.NaCl aggravates the hot corrosion through self ustaining cycles of chlorination/oxidation.β-NiAl phase fails first as a diffusion channel for the corrosive medium.Significant element interdiffusion occurs.An interdiffusion zone and a secondary reaction zone are formed.Interdiffusion changes the percentage of elements,causing a phase transition of the coating.The volume change caused by the phase transition induces bulging and cracking of the oxide film.Furthermore,the oxidation,hot corrosion,and interdiffusion mechanisms are discussed.
基金supported by the National Key Research and Development Program of China(No.2022YFA1602200)the National Natural Science Foundation of China(Nos.12341501 and 12405174)the Hefei Comprehensive National Science Center for the strong support on the STCF key technology research project.
文摘Electron-positron colliders operating in the GeV center-of-mass range,or tau-charm energy region,have been proved to enable competitive frontier research due to several unique features.With the progress of high-energy physics in the last two decades,a new-generation Tau-Charm factory,called the Super Tau-Charm Facility(STCF),has been actively promoted by the particle physics community in China.STCF has the potential to address fundamental questions such as the essence of color confinement and the matter-antimatter asymmetry within the next decades.The main design goals of the STCF are a center-of-mass energy ranging from 2 to 7 GeV and a luminosity surpassing 5×10^(34)cm^(−2)s^(−1)that is optimized at a center-of-mass energy of 4 GeV,which is approximately 50 times that of the currently operating Tau-Charm factory-BEPCII.The STCF accelerator has two main parts:a double-ring collider with a crab-waist collision scheme and an injector that provides top-up injections for both electron and positron beams.As a typical third-generation electron-positron circular collider,the STCF accelerator faces many challenges in both accelerator physics and technology.In this paper,the conceptual design of the STCF accelerator complex is presented,including the ongoing efforts and plans for technological research and develop-ment,as well as the required infrastructure.The STCF project aims to secure support from the Chinese central government for its construction during the 15th Five-Year Plan(2026-2030).
基金funded by the National Natural Science Foundation of China Instrumentation Program(52327806)Youth Fund of the National Nature Foundation of China(62405020)China Postdoctoral Science Foundation(2024M764131).
文摘Large-aperture optical components are of paramount importance in domains such as integrated circuits,photolithography,aerospace,and inertial confinement fusion.However,measuring their surface profiles relies predominantly on the phase-shifting approach,which involves collecting multiple interferograms and imposes stringent demands on environmental stability.These issues significantly hinder its ability to achieve real-time and dynamic high-precision measurements.Therefore,this study proposes a high-precision large-aperture single-frame interferometric surface profile measurement(LA-SFISPM)method based on deep learning and explores its capability to realize dynamic measurements with high accuracy.The interferogram is matched to the phase by training the data measured using the small aperture.The consistency of the surface features of the small and large apertures is enhanced via contrast learning and feature-distribution alignment.Hence,high-precision phase reconstruction of large-aperture optical components can be achieved without using a phase shifter.The experimental results show that for the tested mirror withΦ=820 mm,the surface profile obtained from LA-SFISPM is subtracted point-by-point from the ground truth,resulting in a maximum single-point error of 4.56 nm.Meanwhile,the peak-to-valley(PV)value is 0.0758λ,and the simple repeatability of root mean square(SR-RMS)value is 0.00025λ,which aligns well with the measured results obtained by ZYGO.In particular,a significant reduction in the measurement time(reduced by a factor of 48)is achieved compared with that of the traditional phase-shifting method.Our proposed method provides an efficient,rapid,and accurate method for obtaining the surface profiles of optical components with different diameters without employing a phase-shifting approach,which is highly desired in large-aperture interferometric measurement systems.
基金Supported by National Key Research and Development Program of China(Grant No.2022YFC2805703)National Natural Science Foundation of China(Grant Nos.52305073,51975507).
文摘Thermosyphon loops are widely used in cooling systems.However,such distributed thermal management systems lack the ability to actively control the coolant flow in each parallel branch.An effective method for addressing this is to control the coolant flow in each branch using a solenoid valve.However,the existing valves do not satisfy the requirements for fast switching,low power,low pressure loss,and miniaturization.Therefore,in this study,a low-power-consumption miniature solenoid valve(LMSV)is proposed for use in thermal management systems.The key novelty is that the valve is designed with a suitably sized permanent magnet(PM)to allow the spool to continue working without consuming electrical energy.To achieve low flow resistance,a straight-through design is employed in the valve with the electromagnetic actuator located inside the valve shell.Multiphysical coupling analysis is performed to investigate its performance.The influence of the PM dimensions and current on the magnetic field distribution and electromagnetic force is studied.The effects of these key parameters on the flow field and pressure loss are also analyzed.Because the LMSV is sensitive to temperature,the switching time and energy consumption at different working temperatures are investigated.Experimental test platforms are constructed.A valve switching time of as short as 3 ms,pressure loss of 200 Pa at 0.92 L/min,and energy consumption of approximately 1.55 J during the opening and closing processes are achieved.The novel solenoid valve proposed in this study offers fast switching,low power consumption,low pressure loss,and miniaturization to meet the requirements of thermal management systems.
基金Natural Science Research Project of Education Department of Anhui Province of China,Grant/Award Number:2023AH051020Key Project of Anhui Province's Science and Technology Innovation Tackle Plan,Grant/Award Number:202423k09020040+3 种基金National Key Research and Development Program of China,Grant/Award Number:2023YFD1802200Natural Science Foundation of Anhui Province,Grant/Award Number:2308085MF21National Natural Science Foundation of China,Grant/Award Numbers:32472007,62301006,62306008University Synergy Innovation Program of Anhui Province,Grant/Award Number:GXXT-2022-046。
文摘In the era of big data,personalised recommendation systems are essential for enhancing user engagement and driving business growth.However,traditional recommendation algorithms,such as collaborative filtering,face significant challenges due to data sparsity,algorithm scalability,and the difficulty of adapting to dynamic user preferences.These limitations hinder the ability of systems to provide highly accurate and personalised recommendations.To address these challenges,this paper proposes a clustering-based recommendation method that integrates an enhanced Grasshopper Optimisation Algorithm(GOA),termed LCGOA,to improve the accuracy and efficiency of recommendation systems by optimising cluster centroids in a dynamic environment.By combining the K-means algorithm with the enhanced GOA,which incorporates a Lévy flight mechanism and multi-strategy co-evolution,our method overcomes the centroid sensitivity issue,a key limitation in traditional clustering techniques.Experimental results across multiple datasets show that the proposed LCGOA-based method significantly outperforms conventional recommendation algorithms in terms of recommendation accuracy,offering more relevant content to users and driving greater customer satisfaction and business growth.
基金the National Natural Science Foundation of China(U21A20376,82102871,81988101,81903184,81790633,and 81830054)the Innovation Program of Shanghai Municipal Education Commission(2019-01-07-00-07E00065)+1 种基金the National Science Foundation of Shanghai(21XD1404600,21JC1406600,and 22140901000)the China Postdoctoral Science Foundation(2020M671007).
文摘The application of tumor antigen-based immunotherapy is hindered by the rarity of validated immunogenic peptides.In this study,we aimed to investigate the potential of circular RNAs(circRNAs)as a novel source of tumor antigen peptides in hepatobiliary tumor organoids.Using RNA-sequencing(RNA-seq)with an algorithm-based score tool,3950 translated tumor-specific circRNAs were predicted to generate 18971 antigen peptides in 27 organoids.In view of the antigen landscape,11 amino acid length(mer)peptides and human leukocyte antigen(HLA)-A binding peptides harbored the highest immunogenicity-related scores.In three out of five analyzed organoids,13 predicted antigen peptides were directly confirmed as HLA-A,-B,and-C(HLA-ABC)binding peptides with mass spectrometry(MS)-based immunopeptidomics.CircRNA-derived tumor-specific peptides presented by the HLA-ABC molecules stimulated cluster of differentiation 8(CD8)T cells to exhibit increased CD107a interferonγ(IFNγ)co-expressions and IFNγsecretion in flow cytometry and enzyme-linked immunosorbent assay(ELISA).Cytotoxic T cell activity targeting the organoids,induced by the immunogenic circRNA-derived peptides,was verified in a killing assay.Notably,the antigen peptide YGFNEILKK from circTBC1D15 was not only recognized as an HLA-ABC-presented peptide of the organoids but also drastically reduced the tumor organoid survival rate.Our findings highlight a crucial subset for generating tumor antigens,which has implications for targeting tumor-specific circRNAs in cancers.
