Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangle...Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the brain.The NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and aggregation.Because NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines.Here,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau phosphorylation.Using biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons.In primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis present.In the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical neurons.Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses.We also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced responses.These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in neurons.Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.展开更多
The meteor radar can detect the zenith angle,azimuth,radial velocity,and altitude of meteor trails so that one can invert the wind profiles in the mesosphere and low thermosphere(MLT)region,based on the Interferometri...The meteor radar can detect the zenith angle,azimuth,radial velocity,and altitude of meteor trails so that one can invert the wind profiles in the mesosphere and low thermosphere(MLT)region,based on the Interferometric and Doppler techniques.In this paper,the horizontal wind field,gravity wave(GW)disturbance variance,and GW fluxes are analyzed through the meteor radar observation from 2012−2022,at Mohe(53.5°N,122.4°E)and Zuoling(30.5°N,114.6°E)stations of the(Chinese)Meridian Project.The Lomb−Scargle periodogram method has been utilized to analyze the periodic variations for time series with observational data gaps.The results show that the zonal winds at both stations are eastward dominated,while the meridional winds are southward dominated.The variance of GW disturbances in the zonal and meridional directions increases gradually with height,and there is a strong pattern of annual variation.The zonal momentum flux of GW changes little with height,showing weak annual variation.The meridional GW flux varies gradually from northward to southward with height,and the annual periodicity is stronger.For both stations,the maximum values of zonal and meridional wind occur close to the peak heights of GW flux,with opposite directions.This observational evidence is consistent with the filtering theory.The horizontal wind velocity,GW flux,and disturbance variance of the GW at Mohe are overall smaller than those at Zuoling,indicating weaker activities in the MLT at Mohe.The power spectral density(PSD)calculated by the Lomb−Scargle periodogram shows that there are 12-month period and 6-month period in horizontal wind field,GW disturbance variance and GW flux at both stations,and especially there is also a 4-month cycle in the disturbance variance.The PSD of the 12-month and 6-month cycles exhibits maximum values below 88 km and above 94 km.展开更多
Dear Editor,This letter focuses on how an attacker can design suitable improved zero-dynamics (ZD) attack signal based on state estimates of target system. Improved ZD attack is to change zero dynamic gain matrix of a...Dear Editor,This letter focuses on how an attacker can design suitable improved zero-dynamics (ZD) attack signal based on state estimates of target system. Improved ZD attack is to change zero dynamic gain matrix of attack signal to a matrix with determinant greater than 1.展开更多
The distillation process is an important chemical process,and the application of data-driven modelling approach has the potential to reduce model complexity compared to mechanistic modelling,thus improving the efficie...The distillation process is an important chemical process,and the application of data-driven modelling approach has the potential to reduce model complexity compared to mechanistic modelling,thus improving the efficiency of process optimization or monitoring studies.However,the distillation process is highly nonlinear and has multiple uncertainty perturbation intervals,which brings challenges to accurate data-driven modelling of distillation processes.This paper proposes a systematic data-driven modelling framework to solve these problems.Firstly,data segment variance was introduced into the K-means algorithm to form K-means data interval(KMDI)clustering in order to cluster the data into perturbed and steady state intervals for steady-state data extraction.Secondly,maximal information coefficient(MIC)was employed to calculate the nonlinear correlation between variables for removing redundant features.Finally,extreme gradient boosting(XGBoost)was integrated as the basic learner into adaptive boosting(AdaBoost)with the error threshold(ET)set to improve weights update strategy to construct the new integrated learning algorithm,XGBoost-AdaBoost-ET.The superiority of the proposed framework is verified by applying this data-driven modelling framework to a real industrial process of propylene distillation.展开更多
The review by Bangolo et al highlights the role of the gut microbiome in cancerassociated anemia(CAA).However,the impact of microbiome-derived metabolites is underexplored.In this letter,we focus on short-chain fatty ...The review by Bangolo et al highlights the role of the gut microbiome in cancerassociated anemia(CAA).However,the impact of microbiome-derived metabolites is underexplored.In this letter,we focus on short-chain fatty acids,tryptophan metabolites,and polyamines as key mediators linking dysbiosis to impaired erythropoiesis and iron homeostasis.We also propose a research framework that integrates multi-omics analysis and gnotobiotic models.Finally,we discuss the clinical potential of metabolite-based diagnostics and microbiome-targeted therapies in managing CAA.展开更多
Cation segregation on cathode surfaces plays a key role in determining the activity and operational stability of solid oxide fuel cells(SOFCs).The double perovskite oxide PrBa_(0.8)Ca_(0.2)Co_(2)O_(5+δ)(PBCC)has been...Cation segregation on cathode surfaces plays a key role in determining the activity and operational stability of solid oxide fuel cells(SOFCs).The double perovskite oxide PrBa_(0.8)Ca_(0.2)Co_(2)O_(5+δ)(PBCC)has been widely studied as an active cathode but still suffer from serious detrimental segregations.To enhance the cathode stability,a PBCC derived A-site medium-entropy Pr_(0.6)La_(0.1)Nd_(0.1)Sm_(0.1)Gd_(0.1)Ba_(0.8)Ca_(0.2)Co_(2)O_(5+δ)(ME-PBCC)oxide was prepared and its segregation behaviors were investigated under different conditions.Compared with initial PBCC oxide,the segregations of BaO and Co_(3)O_(4)on the surface of ME-PBCC material are significantly suppressed,especially for Co_(3)O_(4),which is attributed to its higher configuration entropy.Our results also confirm the improved electrochemical performance and structural stability of ME-PBCC material,enabling it as a promising cathode for SOFCs.展开更多
To solve the serious volume expansion problem of Sb-based anode materials in the alloying/dealloying process,a strategy combining electrospinning and hydrogen reduction is proposed to prepare a series of Sb-based allo...To solve the serious volume expansion problem of Sb-based anode materials in the alloying/dealloying process,a strategy combining electrospinning and hydrogen reduction is proposed to prepare a series of Sb-based alloys/carbon nanofiber composites(SbM/CNFs,M=Co,Zn,Ni).Inactive elements are innovatively introduced to form Sb based alloys with enhanced stability.The results show that the content of SbCo nanoparticles is high to 69.12%(mass),which are uniformly dispersed in carbon fibers.When evaluated as anode material for SIBs,SbCo/CNFs anode exhibits excellent sodium storage capacity,the initial discharge capacity is 580.0 mA h·g^(-1)at 0.1 A g^(-1),which can hold 483.5 mA h·g^(-1)after 100 cycles.Even the current density increases to 1.0 A g^(-1),the specific capacity still maintains at 344.5 mA h·g^(-1)after 150 cycles.The improved sodium storage capacity is attributed to the synergistic effect of conductive carbon fibers and SbCo nanoparticles with uniform dispersion,which not only provide excellent electronic conductivity,but also enhance structural stability to reduce volume change.展开更多
Esophageal squamous cell carcinoma(ESCC)remains a daunting global health concern.It is marked by aggressive progression and poor survival.While immunotherapy has emerged as a promising treatment modality,both primary ...Esophageal squamous cell carcinoma(ESCC)remains a daunting global health concern.It is marked by aggressive progression and poor survival.While immunotherapy has emerged as a promising treatment modality,both primary and acquired resistance continue to limit its clinical impact,leaving many patients without durable benefits(e.g.,CheckMate-648,ESCORT-1st).This review explains resistance mechanisms and suggests new strategies to improve outcomes.These mechanisms include immunosuppressive cells(Treg cells,myeloid-derived suppressor cells),inhibitory cytokines,molecular alterations involving programmed death 1/programmed death-ligand 1 signaling,and impaired antigen presentation.We also highlight key clinical trials—for example,CheckMate-648 and ESCORT-1st—that reveal both the potential and pitfalls of current immune checkpoint blockade strategies,underscoring the need for robust predictive biomarkers.Moreover,we examine cutting-edge tactics to overcome resistance,including combination regimens,tumor microenvironment remodeling,and tailored treatment approaches rooted in the patient’s unique genomic and immunologic landscape.展开更多
Coal pillars are critical supporting structures between underground coal gasification gasifiers.Its bearing capacity and structural stability are severely threatened by high-temperature environments.To elucidate the h...Coal pillars are critical supporting structures between underground coal gasification gasifiers.Its bearing capacity and structural stability are severely threatened by high-temperature environments.To elucidate the high-temperature deterioration mechanism of coal pillars at multiple scales,coal strength features as a function of temperature were investigated via uniaxial compression and acoustic emission equipment.The pyrolysis reaction process and microstructure evolution were characterized via X-ray diffractometer(XRD),scanning electron microscope(SEM),thermogravimetric(TG),Fourier transform infrared spectroscopy(FTIR),and computed tomography(CT)tests.Experimental results reveal a critical temperature threshold of 500℃for severe degradation of the coal bearing capacity.Specifically,both the strength and elastic modulus exhibit accelerated degradation above this temperature,with maximum reductions of 45.53%and 61.34%,respectively.Above 500℃,coal essentially undergoes a pyrolysis reaction under N_(2)and CO_(2)atmospheres.High temperatures decrease the quantity of O_(2)-based functional groups,growing aromaticity and the degree of graphitization.These changes induce dislocation and slip inside the coal crystal nucleus and then lead to deformation of the coal molecular structural units and strain energy generation.This process results in a great increase in porosity.Consequently,the stress deformation of coal increases,transforming the type of failure from brittle to ductile failure.These findings are expected to provide scientific support for UCG rock strata control.展开更多
With the rise of data-intensive research,data literacy has become a critical capability for improving scientific data quality and achieving artificial intelligence(AI)readiness.In the biomedical domain,data are charac...With the rise of data-intensive research,data literacy has become a critical capability for improving scientific data quality and achieving artificial intelligence(AI)readiness.In the biomedical domain,data are characterized by high complexity and privacy sensitivity,calling for robust and systematic data management skills.This paper reviews current trends in scientific data governance and the evolving policy landscape,highlighting persistent challenges such as inconsistent standards,semantic misalignment,and limited awareness of compliance.These issues are largely rooted in the lack of structured training and practical support for researchers.In response,this study builds on existing data literacy frameworks and integrates the specific demands of biomedical research to propose a comprehensive,lifecycle-oriented data literacy competency model with an emphasis on ethics and regulatory awareness.Furthermore,it outlines a tiered training strategy tailored to different research stages—undergraduate,graduate,and professional,offering theoretical foundations and practical pathways for universities and research institutions to advance data literacy education.展开更多
Assessing regional economic development is key for advancing towards the Sustainable Development Goals and ensuring sustainable societal progress.Traditional evaluation methods focus on basic economic metrics like pop...Assessing regional economic development is key for advancing towards the Sustainable Development Goals and ensuring sustainable societal progress.Traditional evaluation methods focus on basic economic metrics like population and capital,which may not fully reflect the complexities of economic activities.Nighttime light(NTL)has been validated as an alternative indicator for regional economic development,yet limitations persist in its evaluation.This study integrates OpenStreetMap(OSM)data and NTL data,providing a novel data integration approach for evaluating economic development.The study uses mainland of China as a case,applying ordinary least squares(OLS)and geographically weighted regression(GWR)to evaluate OSM and NTL data across provincial,municipal,and county levels.It compares OSM,NTL,and their combined use,providing key empirical insights for enhancing data fusion models.The study results reveal:(1)NTL data is more accurate for provincial-level economic activity,while OSM data excels at the county level.(2)GWR demonstrates superior capability over OLS in revealing the spatial dynamics of economic development across scales.(3)Through the integration of both datasets,it is observed that,compared to single-data modeling,the performance is enhanced at the city scale and county scale.The study demonstrates that combining OSM and NTL data effectively assesses economic development in both developed and underdeveloped areas at provincial,municipal,and county levels.The study offers a straightforward and efficient approach to data integration.The findings offer new research perspectives and scientific support for sustainable regional economic growth,particularly valuable in data-scarce,underdeveloped areas.展开更多
Porcine epidemic diarrhea virus(PEDV)infection causes acute watery diarrhea in neonatal piglets,leading to substantial economic losses within the pig farming industry.This study demonstrates that clofazimine(CFZ)signi...Porcine epidemic diarrhea virus(PEDV)infection causes acute watery diarrhea in neonatal piglets,leading to substantial economic losses within the pig farming industry.This study demonstrates that clofazimine(CFZ)significantly inhibits PEDV replication in a dose-dependent manner in vitro,with negligible cytotoxicity.Findings from our time-of-addition assays indicate that CFZ effectively disrupts multiple stages of the viral infection cycle.Using a CoV-RdRp-Gluc reporter system,we evaluated the potency of CFZ against PEDV RNA-dependent RNA polymerase(RdRp),and determined a low IC50 value of 0.1364μM.Molecular docking studies further confirmed that CFZ has high binding affinity at the active sites of the spike protein and RdRp protein in PEDV.Transcriptome analysis of Vero E6 cells,with and without CFZ treatment,revealed a significant change in transcriptional activity at 8 h postinfection(hpi).Moreover,the simultaneous application of CFZ and nucleoside analogs showed enhanced the anti-PEDV effect of CFZ in vitro.Our study underscores the potential of CFZ as a viable therapeutic agent against PEDV.展开更多
Anion exchange membranes(AEMs)combining high hydroxide conductivity and alkali-resistant stability have become a major challenge for the long-term development of anion exchange membrane fuel cells(AEMFCs).Here,we desi...Anion exchange membranes(AEMs)combining high hydroxide conductivity and alkali-resistant stability have become a major challenge for the long-term development of anion exchange membrane fuel cells(AEMFCs).Here,we designed a series of poly(mequitazine-terphenyl piperidinium)(QPMTP-X)AEMs with dual-functionalized quaternary ammonium cations by introducing a certain proportion of large steric hindrance mequitazine(MEQ)molecular building unit into the poly(aryl piperidinium)backbone.QPMTP-X retains the excellent mechanical properties of the poly(aryl piperidinium),while also combining the alkaline stability and high ionic conductivity exhibited by MEQ with flexible quinuclidinium side chains,achieving an overall improvement of membrane performance.Notably,QPMTP-30 exhibits an ultra-high conductivity of up to 206.83 mS cm^(-1)and excellent alkaline stability(over 95%conductivity is maintained after 1000 h of conditioning in 2 M NaOH at 80℃).In fuel cell performance test,QPMTP-30 achieves a peak power density(PPD)of 974.5 mW cm^(-2)and operates stably at 80℃for more than 60 h(0.1 A cm^(-2)).Incorporating large steric hindrance building blocks and multi-cations into the poly(aryl piperidinium)backbone not only synergizes the development of highperformance AEMs but also opens up new ideas for the structural design of future AEMs.展开更多
Ammonia(NH_(3))is a fundamental chemical in agriculture and an ideal hydrogen carrier.Consequently,NH_(3)synthesis strategies with high efficiency,energy conservation,environmental friendliness,and sustainability are ...Ammonia(NH_(3))is a fundamental chemical in agriculture and an ideal hydrogen carrier.Consequently,NH_(3)synthesis strategies with high efficiency,energy conservation,environmental friendliness,and sustainability are desired eminently.The nitrite(NO_(2)^(-))reduction reaction(NO_(2-)RR)to NH_(3)offers a feasibly low-energy consumption and continuable approach to replace industrial NH_(3)synthesis.Herein,polyethyleneimine(PEI)modified Au core Rh shell nanodendrites(Au@Rh-NDs)nanohybrid(Au@Rh-NDs/PEI)with branched structure is synthesized,which achieves the high NH_(3)yield(1.68 mg h^(-1)mg_(cat)^(-1))and Faradaic efficiency(FE)of 95.86%for NO_(2)^(-)-RR at-0.39 V potential in neutral electrolyte.Particularly,the introduction of PEI significantly enhances the electroactivity of Au@Rh-NDs at low concentration of 1 mM NaNO_(2),which originates from the enrichment function of PEI for NO_(2)^(-)-ion.In addition,the Au basement permits the sustainable solar power to expedite the NO_(2)^(-)-RR at Au@Rh-NDs/PEI owing to the localized surface plasmon resonance(LSPR)of the Au core substrate.This work may provide an admissible tactic to build excellent catalysts on account of organic molecule-mediated interfacial engineering in a variety of fields of catalysis and electrocatalysis.展开更多
Background:Colorectal cancer(CRC)is common and deadly,often leading to metastasis,challenging treatment,and poor outcomes.Understanding its molecular basis is crucial for developing effective therapies.Aims:This study...Background:Colorectal cancer(CRC)is common and deadly,often leading to metastasis,challenging treatment,and poor outcomes.Understanding its molecular basis is crucial for developing effective therapies.Aims:This study aimed to investigate the role of Myosin Heavy Chain 11(MYH11)in CRC progression,especially its effects on epithelial-mesenchymal transition(EMT)and cell behavior,and to explore its potential regulation by the EMT transcription factor zinc finger E-box binding homeobox 1(ZEB1).Methods:Differential expression analysis was performed in the GSE123390 and TCGA-READ datasets,and 317 intersection genes were identified.The hub gene MYH11 was identified based on Protein-protein interaction(PPI)analysis and expression validation.The effects of MYH11 and the EMT transcription factor(ZEB1)on the behavior of CRC cells were investigated in vitro.Results:Bioinformatics research revealed that MYH11 was considerably downregulated in CRC samples as compared to normal samples.Overexpression of MYH11 inhibited the proliferation,migration,and invasion of CRC cells.Western blotting(WB)testing showed that MYH11 overexpression inhibited EMT by elevating E-cadherin levels while suppressing ZEB1,vimentin,and N-cadherin expressions.By contrast,overexpression of ZEB1 promoted EMT and enhanced migration,invasion,and proliferation of CRC cells.The negative impacts of MYH11 affecting EMT markers and cell behaviors were partially mitigated by co-overexpression of MYH11 and ZEB1,indicating that MYH11 regulates EMT and CRC progression through ZEB1.Conclusion:Our study shows MYH11 curbs CRC growth by blocking EMT and invasion,but ZEB1 overexpression reduces this effect.It uncovers key CRC pathways and suggests MYH11’s therapeutic potential.展开更多
Pentadactyl limbs represent a conserved morphological feature among tetrapods,with anterior digits considered more important than posterior digits for refined movement.While posterior digit formation is governed by gr...Pentadactyl limbs represent a conserved morphological feature among tetrapods,with anterior digits considered more important than posterior digits for refined movement.While posterior digit formation is governed by graded expression of the Shh and 5’Hox genes,the regulatory mechanisms underlying anterior digit development,especially digit I(DI),remain poorly defined.This study identified an anterior expression pattern of Zic3 in the limb buds of representative tetrapods,including humans,which exerted an inhibitory effect on skeletal development.Zic3 was highly expressed in the anterior region of limb buds at early developmental stages,with species-specific divergence emerging during later development.Overexpression of Zic3 significantly delayed chondrogenesis and ossification,leading to bone shortening but not loss.Furthermore,RNA sequencing demonstrated that Zic3 down-regulated key genes associated with skeletal development,including Cytl1,Sox9,Ihh,Ptch1,Runx2,and Wnt16.These findings demonstrate that Zic3 acts as a conserved inhibitor of anterior skeletal maturation and contributes to the molecular asymmetry of tetrapod limb development.展开更多
The original monitoring data from aero-engines possess characteristics such as high dimen-sionality,strong noise,and imbalance,which present substantial challenges to traditional anomalydetection methods.In response,t...The original monitoring data from aero-engines possess characteristics such as high dimen-sionality,strong noise,and imbalance,which present substantial challenges to traditional anomalydetection methods.In response,this paper proposes a method based on Fuzzy Fusion of variablesand Discriminant mapping of features for Clustering(FFD-Clustering)to detect anomalies in originalmonitoring data from Aircraft Communication Addressing and Reporting System(ACARS).Firstly,associated variables are fuzzily grouped to extract the underlying distribution characteristics and trendsfrom the data.Secondly,a multi-layer contrastive denoising-based feature Fusion Encoding Network(FEN)is designed for each variable group,which can construct representative features for each variablegroup through eliminating strong noise and complex interrelations between variables.Thirdly,a featureDiscriminative Mapping Network(DMN)based on reconstruction difference re-clustering is designed,which can distinguish dissimilar feature vectors when mapping representative features to a unified fea-ture space.Finally,the K-means clustering is used to detect the abnormal feature vectors in the unifiedfeature space.Additionally,the algorithm is capable of reconstructing identified abnormal vectors,thereby locating the abnormal variable groups.The performance of this algorithm was tested ontwo public datasets and real original monitoring data from four aero-engines'ACARS,demonstratingits superiority and application potential in aero-engine anomaly detection.展开更多
Background:Hepatocellular carcinoma(HCC)is one of the most prevalent malignant tumors worldwide,and endocrine,metabolic,and immune factors influence its occurrence and progression.Hypothyroidism(HT)is a common endocri...Background:Hepatocellular carcinoma(HCC)is one of the most prevalent malignant tumors worldwide,and endocrine,metabolic,and immune factors influence its occurrence and progression.Hypothyroidism(HT)is a common endocrine disorder that may affect cancer risk;however,its relationship with HCC remains unclear.Objective:This study aimed to investigate the potential molecular and immune mechanisms underlying the association between HT and HCC,with a focus on the regulatory effects of HT-related genetic variants on the hepatic tumor immune microenvironment.Methods:Single-nucleotide polymorphisms(SNPs)associated with HT and HCC identified through Mendelian randomization were functionally annotated using the Ensembl Genome Browser and mapped to candidate genes.Functional enrichment and pathway analyses were performed with Metascape.Differentially expressed target genes between HCC and normal liver tissues were screened using GEPIA2,and their protein expression levels were validated in the Human Protein Atlas(HPA)database.The association between target gene expression and immune cell infiltration was further evaluated using TIMER2.0.Results:A total of 68 candidate genes were analyzed.Enrichment analysis revealed that these genes are involved in IFN-γ-mediated immune responses,PI3K/AKT and RAC1 signaling pathways,and other immune regulatory processes.Among them,HLA-DQA1,HLA-DPB1,HLA-DQA2,and PVT1 showed significant differential expression in HCC.HLA-DQA1,HLA-DPB1,and HLA-DQA2 were positively correlated with CD8⁺T cells,regulatory T cells(Tregs),and M2 macrophages,suggesting that these genes may exert bidirectional effects on antitumor immunity and immunosuppression.PVT1 may influence the immune microenvironment by regulating myeloid cell recruitment and extracellular matrix remodeling.Conclusion:HLA-DQA1,HLA-DPB1,HLA-DQA2,and PVT1 may reduce the risk of HCC by enhancing IFN-γ-mediated antitumor immunity and modulating key signaling pathways,while also contributing to immune microenvironment remodeling.These findings provide mechanistic insights into the protective effects of HT on HCC and suggest potential targets for immunotherapeutic strategies.展开更多
基金supported by a grant from Key Laboratory of Alzheimer's Disease of Zhejiang Province,Institute of Aging,Wenzhou Medical University,No.ZJAD-2021002(to ZW)。
文摘Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the brain.The NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and aggregation.Because NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines.Here,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau phosphorylation.Using biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons.In primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis present.In the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical neurons.Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses.We also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced responses.These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in neurons.Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.
基金supported by the Fundamental Research Funds for the Central Universities,CHD(NO.300102263205 and NO.300102264916)the West Light Cross-Disciplinary Innovation team of Chinese Academy of Sciences(NO.E1294301).supported by the Fundamental Research Funds for the Central Universities,CHD(NO.300102263205 and NO.300102264916)the West Light Cross-Disciplinary Innovation team of Chinese Academy of Sciences(NO.E1294301).
文摘The meteor radar can detect the zenith angle,azimuth,radial velocity,and altitude of meteor trails so that one can invert the wind profiles in the mesosphere and low thermosphere(MLT)region,based on the Interferometric and Doppler techniques.In this paper,the horizontal wind field,gravity wave(GW)disturbance variance,and GW fluxes are analyzed through the meteor radar observation from 2012−2022,at Mohe(53.5°N,122.4°E)and Zuoling(30.5°N,114.6°E)stations of the(Chinese)Meridian Project.The Lomb−Scargle periodogram method has been utilized to analyze the periodic variations for time series with observational data gaps.The results show that the zonal winds at both stations are eastward dominated,while the meridional winds are southward dominated.The variance of GW disturbances in the zonal and meridional directions increases gradually with height,and there is a strong pattern of annual variation.The zonal momentum flux of GW changes little with height,showing weak annual variation.The meridional GW flux varies gradually from northward to southward with height,and the annual periodicity is stronger.For both stations,the maximum values of zonal and meridional wind occur close to the peak heights of GW flux,with opposite directions.This observational evidence is consistent with the filtering theory.The horizontal wind velocity,GW flux,and disturbance variance of the GW at Mohe are overall smaller than those at Zuoling,indicating weaker activities in the MLT at Mohe.The power spectral density(PSD)calculated by the Lomb−Scargle periodogram shows that there are 12-month period and 6-month period in horizontal wind field,GW disturbance variance and GW flux at both stations,and especially there is also a 4-month cycle in the disturbance variance.The PSD of the 12-month and 6-month cycles exhibits maximum values below 88 km and above 94 km.
基金supported in part by the National Natural Science Foundation of China(61873106,62303109)Start-Up Research Fund of Southeast University(RF1028623002)Shenzhen Science and Technology Program(JCYJ20230807114609019)
文摘Dear Editor,This letter focuses on how an attacker can design suitable improved zero-dynamics (ZD) attack signal based on state estimates of target system. Improved ZD attack is to change zero dynamic gain matrix of attack signal to a matrix with determinant greater than 1.
基金supported by the National Key Research and Development Program of China(2023YFB3307801)the National Natural Science Foundation of China(62394343,62373155,62073142)+3 种基金Major Science and Technology Project of Xinjiang(No.2022A01006-4)the Programme of Introducing Talents of Discipline to Universities(the 111 Project)under Grant B17017the Fundamental Research Funds for the Central Universities,Science Foundation of China University of Petroleum,Beijing(No.2462024YJRC011)the Open Research Project of the State Key Laboratory of Industrial Control Technology,China(Grant No.ICT2024B70).
文摘The distillation process is an important chemical process,and the application of data-driven modelling approach has the potential to reduce model complexity compared to mechanistic modelling,thus improving the efficiency of process optimization or monitoring studies.However,the distillation process is highly nonlinear and has multiple uncertainty perturbation intervals,which brings challenges to accurate data-driven modelling of distillation processes.This paper proposes a systematic data-driven modelling framework to solve these problems.Firstly,data segment variance was introduced into the K-means algorithm to form K-means data interval(KMDI)clustering in order to cluster the data into perturbed and steady state intervals for steady-state data extraction.Secondly,maximal information coefficient(MIC)was employed to calculate the nonlinear correlation between variables for removing redundant features.Finally,extreme gradient boosting(XGBoost)was integrated as the basic learner into adaptive boosting(AdaBoost)with the error threshold(ET)set to improve weights update strategy to construct the new integrated learning algorithm,XGBoost-AdaBoost-ET.The superiority of the proposed framework is verified by applying this data-driven modelling framework to a real industrial process of propylene distillation.
文摘The review by Bangolo et al highlights the role of the gut microbiome in cancerassociated anemia(CAA).However,the impact of microbiome-derived metabolites is underexplored.In this letter,we focus on short-chain fatty acids,tryptophan metabolites,and polyamines as key mediators linking dysbiosis to impaired erythropoiesis and iron homeostasis.We also propose a research framework that integrates multi-omics analysis and gnotobiotic models.Finally,we discuss the clinical potential of metabolite-based diagnostics and microbiome-targeted therapies in managing CAA.
基金Project supported by the National Natural Science Foundation of China(22279025,21773048,52302119)the Fundamental Research Funds for the Central Universities(2023FRFK06005,HIT.NSRIF202204)。
文摘Cation segregation on cathode surfaces plays a key role in determining the activity and operational stability of solid oxide fuel cells(SOFCs).The double perovskite oxide PrBa_(0.8)Ca_(0.2)Co_(2)O_(5+δ)(PBCC)has been widely studied as an active cathode but still suffer from serious detrimental segregations.To enhance the cathode stability,a PBCC derived A-site medium-entropy Pr_(0.6)La_(0.1)Nd_(0.1)Sm_(0.1)Gd_(0.1)Ba_(0.8)Ca_(0.2)Co_(2)O_(5+δ)(ME-PBCC)oxide was prepared and its segregation behaviors were investigated under different conditions.Compared with initial PBCC oxide,the segregations of BaO and Co_(3)O_(4)on the surface of ME-PBCC material are significantly suppressed,especially for Co_(3)O_(4),which is attributed to its higher configuration entropy.Our results also confirm the improved electrochemical performance and structural stability of ME-PBCC material,enabling it as a promising cathode for SOFCs.
基金supported by National Natural Science Foundation of China(22379056,22479065)Industry foresight and common key technology research in Carbon Peak and Carbon Neutrality Special Project from Zhenjiang city(CG2023003)+1 种基金Industry-University-Research Cooperation Project of Jiangsu Province(BY20230347)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(24KJB150008).
文摘To solve the serious volume expansion problem of Sb-based anode materials in the alloying/dealloying process,a strategy combining electrospinning and hydrogen reduction is proposed to prepare a series of Sb-based alloys/carbon nanofiber composites(SbM/CNFs,M=Co,Zn,Ni).Inactive elements are innovatively introduced to form Sb based alloys with enhanced stability.The results show that the content of SbCo nanoparticles is high to 69.12%(mass),which are uniformly dispersed in carbon fibers.When evaluated as anode material for SIBs,SbCo/CNFs anode exhibits excellent sodium storage capacity,the initial discharge capacity is 580.0 mA h·g^(-1)at 0.1 A g^(-1),which can hold 483.5 mA h·g^(-1)after 100 cycles.Even the current density increases to 1.0 A g^(-1),the specific capacity still maintains at 344.5 mA h·g^(-1)after 150 cycles.The improved sodium storage capacity is attributed to the synergistic effect of conductive carbon fibers and SbCo nanoparticles with uniform dispersion,which not only provide excellent electronic conductivity,but also enhance structural stability to reduce volume change.
文摘Esophageal squamous cell carcinoma(ESCC)remains a daunting global health concern.It is marked by aggressive progression and poor survival.While immunotherapy has emerged as a promising treatment modality,both primary and acquired resistance continue to limit its clinical impact,leaving many patients without durable benefits(e.g.,CheckMate-648,ESCORT-1st).This review explains resistance mechanisms and suggests new strategies to improve outcomes.These mechanisms include immunosuppressive cells(Treg cells,myeloid-derived suppressor cells),inhibitory cytokines,molecular alterations involving programmed death 1/programmed death-ligand 1 signaling,and impaired antigen presentation.We also highlight key clinical trials—for example,CheckMate-648 and ESCORT-1st—that reveal both the potential and pitfalls of current immune checkpoint blockade strategies,underscoring the need for robust predictive biomarkers.Moreover,we examine cutting-edge tactics to overcome resistance,including combination regimens,tumor microenvironment remodeling,and tailored treatment approaches rooted in the patient’s unique genomic and immunologic landscape.
基金supported by Young Scholar Program(Category A Continuation Funding)of National Natural Science Foundation of China(No.52525401)General Program of National Natural Science Foundation of China(No.52174125)+4 种基金Outstanding Youth Cultivation Project in Shanxi Province(No.202103021222008)Major Program of National Natural Science Foundation of China(No.52334005)New Cornerstone Science Foundation through the XPLORER PRIZEShanxi-Zheda Institute of Advanced Materials and Chemical Engineering(No.2022SX-TD010)Shanxi Science and Technology Major Project(No.20201102004).
文摘Coal pillars are critical supporting structures between underground coal gasification gasifiers.Its bearing capacity and structural stability are severely threatened by high-temperature environments.To elucidate the high-temperature deterioration mechanism of coal pillars at multiple scales,coal strength features as a function of temperature were investigated via uniaxial compression and acoustic emission equipment.The pyrolysis reaction process and microstructure evolution were characterized via X-ray diffractometer(XRD),scanning electron microscope(SEM),thermogravimetric(TG),Fourier transform infrared spectroscopy(FTIR),and computed tomography(CT)tests.Experimental results reveal a critical temperature threshold of 500℃for severe degradation of the coal bearing capacity.Specifically,both the strength and elastic modulus exhibit accelerated degradation above this temperature,with maximum reductions of 45.53%and 61.34%,respectively.Above 500℃,coal essentially undergoes a pyrolysis reaction under N_(2)and CO_(2)atmospheres.High temperatures decrease the quantity of O_(2)-based functional groups,growing aromaticity and the degree of graphitization.These changes induce dislocation and slip inside the coal crystal nucleus and then lead to deformation of the coal molecular structural units and strain energy generation.This process results in a great increase in porosity.Consequently,the stress deformation of coal increases,transforming the type of failure from brittle to ductile failure.These findings are expected to provide scientific support for UCG rock strata control.
文摘With the rise of data-intensive research,data literacy has become a critical capability for improving scientific data quality and achieving artificial intelligence(AI)readiness.In the biomedical domain,data are characterized by high complexity and privacy sensitivity,calling for robust and systematic data management skills.This paper reviews current trends in scientific data governance and the evolving policy landscape,highlighting persistent challenges such as inconsistent standards,semantic misalignment,and limited awareness of compliance.These issues are largely rooted in the lack of structured training and practical support for researchers.In response,this study builds on existing data literacy frameworks and integrates the specific demands of biomedical research to propose a comprehensive,lifecycle-oriented data literacy competency model with an emphasis on ethics and regulatory awareness.Furthermore,it outlines a tiered training strategy tailored to different research stages—undergraduate,graduate,and professional,offering theoretical foundations and practical pathways for universities and research institutions to advance data literacy education.
基金funded by The Third Comprehensive Scientific Investigation in Xinjiang(Grant No.2021xjkk1001)Program of National Social Science Foundation of China(Grant No.22BJL061)+1 种基金Major Project of Xinjiang Social Science Foundation(Grant No.21AZD008)The National Natural Science Foundation of China(Grant No.41461035).
文摘Assessing regional economic development is key for advancing towards the Sustainable Development Goals and ensuring sustainable societal progress.Traditional evaluation methods focus on basic economic metrics like population and capital,which may not fully reflect the complexities of economic activities.Nighttime light(NTL)has been validated as an alternative indicator for regional economic development,yet limitations persist in its evaluation.This study integrates OpenStreetMap(OSM)data and NTL data,providing a novel data integration approach for evaluating economic development.The study uses mainland of China as a case,applying ordinary least squares(OLS)and geographically weighted regression(GWR)to evaluate OSM and NTL data across provincial,municipal,and county levels.It compares OSM,NTL,and their combined use,providing key empirical insights for enhancing data fusion models.The study results reveal:(1)NTL data is more accurate for provincial-level economic activity,while OSM data excels at the county level.(2)GWR demonstrates superior capability over OLS in revealing the spatial dynamics of economic development across scales.(3)Through the integration of both datasets,it is observed that,compared to single-data modeling,the performance is enhanced at the city scale and county scale.The study demonstrates that combining OSM and NTL data effectively assesses economic development in both developed and underdeveloped areas at provincial,municipal,and county levels.The study offers a straightforward and efficient approach to data integration.The findings offer new research perspectives and scientific support for sustainable regional economic growth,particularly valuable in data-scarce,underdeveloped areas.
基金supported by a grant from the National Key Research and Development Plans of China(No.2021YFD1800401)to Zhe Wangthe National Natural Science Foundation of China(No.32070128)to Zhe Wang+5 种基金the Shanghai Biomedical Science and Technology Support Special Project(No.21S11900200)to Zhe Wangthe National Natural Science Foundation of China(No.31472211)to ZhiBiao Yangthe Natural Science Foundation of Shanghai(No.21ZR1433900)to Zhibiao Yangthe National Key Research and Development Program of China(No.2022YFD1800805)to Yanjun Zhouthe Pinduoduo-China Agricultural University Research Fund(PC2024A01003)to Xiangfeng Wangthe Biomedicine and Technology Supporting Project of the Shanghai Science and Technology Innovation Plan(Grant No.22S11902200,China)to Tao Sun.
文摘Porcine epidemic diarrhea virus(PEDV)infection causes acute watery diarrhea in neonatal piglets,leading to substantial economic losses within the pig farming industry.This study demonstrates that clofazimine(CFZ)significantly inhibits PEDV replication in a dose-dependent manner in vitro,with negligible cytotoxicity.Findings from our time-of-addition assays indicate that CFZ effectively disrupts multiple stages of the viral infection cycle.Using a CoV-RdRp-Gluc reporter system,we evaluated the potency of CFZ against PEDV RNA-dependent RNA polymerase(RdRp),and determined a low IC50 value of 0.1364μM.Molecular docking studies further confirmed that CFZ has high binding affinity at the active sites of the spike protein and RdRp protein in PEDV.Transcriptome analysis of Vero E6 cells,with and without CFZ treatment,revealed a significant change in transcriptional activity at 8 h postinfection(hpi).Moreover,the simultaneous application of CFZ and nucleoside analogs showed enhanced the anti-PEDV effect of CFZ in vitro.Our study underscores the potential of CFZ as a viable therapeutic agent against PEDV.
基金financial support of this work by the Natural Science Foundation of China(Grant Nos.U24A20505,52473205)Chang Bai Mountain Scholars Program of Jilin Province and Jilin Provincial Science&Technology Department(Grant No.YDZJ202401357).
文摘Anion exchange membranes(AEMs)combining high hydroxide conductivity and alkali-resistant stability have become a major challenge for the long-term development of anion exchange membrane fuel cells(AEMFCs).Here,we designed a series of poly(mequitazine-terphenyl piperidinium)(QPMTP-X)AEMs with dual-functionalized quaternary ammonium cations by introducing a certain proportion of large steric hindrance mequitazine(MEQ)molecular building unit into the poly(aryl piperidinium)backbone.QPMTP-X retains the excellent mechanical properties of the poly(aryl piperidinium),while also combining the alkaline stability and high ionic conductivity exhibited by MEQ with flexible quinuclidinium side chains,achieving an overall improvement of membrane performance.Notably,QPMTP-30 exhibits an ultra-high conductivity of up to 206.83 mS cm^(-1)and excellent alkaline stability(over 95%conductivity is maintained after 1000 h of conditioning in 2 M NaOH at 80℃).In fuel cell performance test,QPMTP-30 achieves a peak power density(PPD)of 974.5 mW cm^(-2)and operates stably at 80℃for more than 60 h(0.1 A cm^(-2)).Incorporating large steric hindrance building blocks and multi-cations into the poly(aryl piperidinium)backbone not only synergizes the development of highperformance AEMs but also opens up new ideas for the structural design of future AEMs.
基金supported by the National Natural Science Foundation of China(22273056)the National Training Program of Innovation and Entrepreneurship for Undergraduates(202410718010)+2 种基金the Natural Science Basic Research Project of Shaanxi Province(2024JC-YBQN-0092)the Scientific research project of Shaanxi Institute of Basic Sciences(23JHQ003)the Scientific Research Program Funded by Education Department of Shaanxi Provincial Government(23JK0694)。
文摘Ammonia(NH_(3))is a fundamental chemical in agriculture and an ideal hydrogen carrier.Consequently,NH_(3)synthesis strategies with high efficiency,energy conservation,environmental friendliness,and sustainability are desired eminently.The nitrite(NO_(2)^(-))reduction reaction(NO_(2-)RR)to NH_(3)offers a feasibly low-energy consumption and continuable approach to replace industrial NH_(3)synthesis.Herein,polyethyleneimine(PEI)modified Au core Rh shell nanodendrites(Au@Rh-NDs)nanohybrid(Au@Rh-NDs/PEI)with branched structure is synthesized,which achieves the high NH_(3)yield(1.68 mg h^(-1)mg_(cat)^(-1))and Faradaic efficiency(FE)of 95.86%for NO_(2)^(-)-RR at-0.39 V potential in neutral electrolyte.Particularly,the introduction of PEI significantly enhances the electroactivity of Au@Rh-NDs at low concentration of 1 mM NaNO_(2),which originates from the enrichment function of PEI for NO_(2)^(-)-ion.In addition,the Au basement permits the sustainable solar power to expedite the NO_(2)^(-)-RR at Au@Rh-NDs/PEI owing to the localized surface plasmon resonance(LSPR)of the Au core substrate.This work may provide an admissible tactic to build excellent catalysts on account of organic molecule-mediated interfacial engineering in a variety of fields of catalysis and electrocatalysis.
基金funded by Outstanding Leaders Training Programof Pudong Health Commission of Shanghai(No.PWR12023-03)In-house Project of Shanghai Pudong NewArea People’sHospital(No.E24-02).
文摘Background:Colorectal cancer(CRC)is common and deadly,often leading to metastasis,challenging treatment,and poor outcomes.Understanding its molecular basis is crucial for developing effective therapies.Aims:This study aimed to investigate the role of Myosin Heavy Chain 11(MYH11)in CRC progression,especially its effects on epithelial-mesenchymal transition(EMT)and cell behavior,and to explore its potential regulation by the EMT transcription factor zinc finger E-box binding homeobox 1(ZEB1).Methods:Differential expression analysis was performed in the GSE123390 and TCGA-READ datasets,and 317 intersection genes were identified.The hub gene MYH11 was identified based on Protein-protein interaction(PPI)analysis and expression validation.The effects of MYH11 and the EMT transcription factor(ZEB1)on the behavior of CRC cells were investigated in vitro.Results:Bioinformatics research revealed that MYH11 was considerably downregulated in CRC samples as compared to normal samples.Overexpression of MYH11 inhibited the proliferation,migration,and invasion of CRC cells.Western blotting(WB)testing showed that MYH11 overexpression inhibited EMT by elevating E-cadherin levels while suppressing ZEB1,vimentin,and N-cadherin expressions.By contrast,overexpression of ZEB1 promoted EMT and enhanced migration,invasion,and proliferation of CRC cells.The negative impacts of MYH11 affecting EMT markers and cell behaviors were partially mitigated by co-overexpression of MYH11 and ZEB1,indicating that MYH11 regulates EMT and CRC progression through ZEB1.Conclusion:Our study shows MYH11 curbs CRC growth by blocking EMT and invasion,but ZEB1 overexpression reduces this effect.It uncovers key CRC pathways and suggests MYH11’s therapeutic potential.
基金supported by the Department of Science&Technology of Liaoning Province(2024-MS-099,2024-BS-093)。
文摘Pentadactyl limbs represent a conserved morphological feature among tetrapods,with anterior digits considered more important than posterior digits for refined movement.While posterior digit formation is governed by graded expression of the Shh and 5’Hox genes,the regulatory mechanisms underlying anterior digit development,especially digit I(DI),remain poorly defined.This study identified an anterior expression pattern of Zic3 in the limb buds of representative tetrapods,including humans,which exerted an inhibitory effect on skeletal development.Zic3 was highly expressed in the anterior region of limb buds at early developmental stages,with species-specific divergence emerging during later development.Overexpression of Zic3 significantly delayed chondrogenesis and ossification,leading to bone shortening but not loss.Furthermore,RNA sequencing demonstrated that Zic3 down-regulated key genes associated with skeletal development,including Cytl1,Sox9,Ihh,Ptch1,Runx2,and Wnt16.These findings demonstrate that Zic3 acts as a conserved inhibitor of anterior skeletal maturation and contributes to the molecular asymmetry of tetrapod limb development.
基金co-supported by the National Science and Technology Major Project,China(No.J2019-I-0001-0001)the National Natural Science Foundation of China(No.52105545)。
文摘The original monitoring data from aero-engines possess characteristics such as high dimen-sionality,strong noise,and imbalance,which present substantial challenges to traditional anomalydetection methods.In response,this paper proposes a method based on Fuzzy Fusion of variablesand Discriminant mapping of features for Clustering(FFD-Clustering)to detect anomalies in originalmonitoring data from Aircraft Communication Addressing and Reporting System(ACARS).Firstly,associated variables are fuzzily grouped to extract the underlying distribution characteristics and trendsfrom the data.Secondly,a multi-layer contrastive denoising-based feature Fusion Encoding Network(FEN)is designed for each variable group,which can construct representative features for each variablegroup through eliminating strong noise and complex interrelations between variables.Thirdly,a featureDiscriminative Mapping Network(DMN)based on reconstruction difference re-clustering is designed,which can distinguish dissimilar feature vectors when mapping representative features to a unified fea-ture space.Finally,the K-means clustering is used to detect the abnormal feature vectors in the unifiedfeature space.Additionally,the algorithm is capable of reconstructing identified abnormal vectors,thereby locating the abnormal variable groups.The performance of this algorithm was tested ontwo public datasets and real original monitoring data from four aero-engines'ACARS,demonstratingits superiority and application potential in aero-engine anomaly detection.
文摘Background:Hepatocellular carcinoma(HCC)is one of the most prevalent malignant tumors worldwide,and endocrine,metabolic,and immune factors influence its occurrence and progression.Hypothyroidism(HT)is a common endocrine disorder that may affect cancer risk;however,its relationship with HCC remains unclear.Objective:This study aimed to investigate the potential molecular and immune mechanisms underlying the association between HT and HCC,with a focus on the regulatory effects of HT-related genetic variants on the hepatic tumor immune microenvironment.Methods:Single-nucleotide polymorphisms(SNPs)associated with HT and HCC identified through Mendelian randomization were functionally annotated using the Ensembl Genome Browser and mapped to candidate genes.Functional enrichment and pathway analyses were performed with Metascape.Differentially expressed target genes between HCC and normal liver tissues were screened using GEPIA2,and their protein expression levels were validated in the Human Protein Atlas(HPA)database.The association between target gene expression and immune cell infiltration was further evaluated using TIMER2.0.Results:A total of 68 candidate genes were analyzed.Enrichment analysis revealed that these genes are involved in IFN-γ-mediated immune responses,PI3K/AKT and RAC1 signaling pathways,and other immune regulatory processes.Among them,HLA-DQA1,HLA-DPB1,HLA-DQA2,and PVT1 showed significant differential expression in HCC.HLA-DQA1,HLA-DPB1,and HLA-DQA2 were positively correlated with CD8⁺T cells,regulatory T cells(Tregs),and M2 macrophages,suggesting that these genes may exert bidirectional effects on antitumor immunity and immunosuppression.PVT1 may influence the immune microenvironment by regulating myeloid cell recruitment and extracellular matrix remodeling.Conclusion:HLA-DQA1,HLA-DPB1,HLA-DQA2,and PVT1 may reduce the risk of HCC by enhancing IFN-γ-mediated antitumor immunity and modulating key signaling pathways,while also contributing to immune microenvironment remodeling.These findings provide mechanistic insights into the protective effects of HT on HCC and suggest potential targets for immunotherapeutic strategies.