BACKGROUND Proteomic signatures of Ming's infiltrative gastric cancer(IGC)remain unknown.AIM To elucidate the molecular characteristics of IGC at the proteomics level.METHODS Twelve pairs of IGC and adjacent norma...BACKGROUND Proteomic signatures of Ming's infiltrative gastric cancer(IGC)remain unknown.AIM To elucidate the molecular characteristics of IGC at the proteomics level.METHODS Twelve pairs of IGC and adjacent normal tissues were collected and their proteomes were analyzed by high performance liquid chromatography tandem mass spectrometry.The identified peptides were sequenced de novo and matched against the SwissProt database using Maxquant software.The differentially expressed proteins(DEPs)were screened using|log2(Fold change)|>1 and P-adj<0.01 as the thresholds.The expression levels of selected proteins were verified by Western blotting.The interaction network of the DEPs was constructed with the STRING database and visualized using Cytoscape with cytoHubba software.The DEPs were functionally annotated using clusterProfiler,STRING and DAVID for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways.P<0.05 was considered statistically significant.RESULTS A total of 7361 DEPs were identified,of which 94 were significantly up-regulated and 223 were significantly down-regulated in IGC relative to normal gastric tissues.The top 10 up-regulated proteins were MRTO4,BOP1,PES1,WDR12,BRIX1,NOP2,POLR1C,NOC2L,MYBBP1A and TSR1,and the top 10 down-regulated proteins were NDUFS8,NDUFS6,NDUFA8,NDUFA5,NDUFC2,NDUFB8,NDUFB5,NDUFB9,UQCRC2 and UQCRC1.The up-regulated proteins were enriched for 9 biological processes including DNA replication,ribosome biogenesis and initiation of DNA replication,and the cellular component MCM complex.Among the down-regulated proteins,17 biological processes were enriched,including glucose metabolism,pyruvic acid metabolism and fatty acidβ-oxidation.In addition,the mitochondrial inner membrane,mitochondrial matrix and mitochondrial proton transport ATP synthase complex were among the 6 enriched cellular components,and 11 molecular functions including reduced nicotinamide adenine dinucleotide dehydrogenase activity,acyl-CoA dehydrogenase activity and nicotinamide adenine dinucleotide binding were also enriched.The significant KEGG pathways for the up-regulated proteins were DNA replication,cell cycle and mismatch repair,whereas 18 pathways including oxidative phosphorylation,fatty acid degradation and phenylalanine metabolism were significantly enriched among the down-regulated proteins.CONCLUSION The proteins involved in cell cycle regulation,DNA replication and mismatch repair,and metabolism were significantly altered in IGC,and the proteomic profile may enable the discovery of novel biomarkers.展开更多
The effect of deformation of porous material on infiltrative performance is investigated. Based on Darcy theory and Boit principle, the Reynolds equation and mathematical expression of deformable metal rubber （MR） m...The effect of deformation of porous material on infiltrative performance is investigated. Based on Darcy theory and Boit principle, the Reynolds equation and mathematical expression of deformable metal rubber （MR） material under laminar flow are obtained according to the change of porosity of metal rubber. It is shown that the throttle of MR material is dependent on its porosity and diameter of metal wires. It will be of great value for the application of MR in throttle field.展开更多
OBJECT:Progression of infiltrative low-grade gliomas(LGGs)has been reported previously.The limitations ofsuch studies include diverse histological grading systems,intervening therapy,and the lack of histological confi...OBJECT:Progression of infiltrative low-grade gliomas(LGGs)has been reported previously.The limitations ofsuch studies include diverse histological grading systems,intervening therapy,and the lack of histological confir-mation of malignant tumor progression.The aim of this study was to determine tumor progression in adult patientswith an initial diagnosis of infiltrative LGG who subsequently underwent a repeated operation,but no other inter-vening therapy.The authors examined factors that may be associated with tumor progression.展开更多
PURPOSE:This study was conducted to investigate the incidence of ERBB1 amplification and overexpression in samples of diffusely infiltrative (WHO grades Ⅱ-Ⅳ) pediatric brain stem glioma (BSG) and determine the relat...PURPOSE:This study was conducted to investigate the incidence of ERBB1 amplification and overexpression in samples of diffusely infiltrative (WHO grades Ⅱ-Ⅳ) pediatric brain stem glioma (BSG) and determine the relationship of these abnormalities to expression and mutation of TP53 and tumor grade. Experimental Design: After central pathology review, the incidence of ERBB1 amplification and overexpression was determined in 28 samples (18 surgical biopsy and 10 postmortem specimens) of BSG using quantitative PCR and immunohistochemistry,展开更多
BACKGROUND Inflammatory indices are considered to be potential prognostic biomarkers for patients with gastric cancer(GC).However,there is no evidence defining the prognostic significance of inflammatory indices for G...BACKGROUND Inflammatory indices are considered to be potential prognostic biomarkers for patients with gastric cancer(GC).However,there is no evidence defining the prognostic significance of inflammatory indices for GC with different tumor infiltrative pattern(INF)types.AIM To evaluate the significance of inflammatory indices and INF types in predicting the prognosis of patients with GC.METHODS A total of 962 patients who underwent radical gastrectomy were retrospectively selected for this study.Patients were categorized into the expansive growth type(INFa),the intermediate type(INFb),and the infiltrative growth type(INFc)groups.The cutoff values of inflammatory indices were analyzed by receiver operating characteristic curves.The Kaplan–Meier method and log-rank test were used to analyze overall survival(OS).The chi-square test was used to analyze the association between inflammatory indices and clinical characteristics.The independent risk factors for prognosis in each group were analyzed by univariate and multivariate analyses based on logistic regression.Nomogram models were constructed by R studio.RESULTS The INFc group had the worst OS(P<0.001).The systemic immune-inflammation index(P=0.039)and metastatic lymph node ratio(mLNR)(P=0.003)were independent risk factors for prognosis in the INFa group.The platelet-lymphocyte ratio(PLR)(P=0.018),age(P=0.026),body mass index(P=0.003),and postsurgical tumor node metastasis(pTNM)stage(P<0.001)were independent risk factors for prognosis in the INFb group.The PLR(P=0.021),pTNM stage(P=0.028),age(P=0.021),and mLNR(P=0.002)were independent risk factors for prognosis in the INFc group.The area under the curve of the nomogram model for predicting 5-year survival in the INFa group,INFb group,and INFc group was 0.787,0.823,and 0.781,respectively.CONCLUSION The outcome of different INF types GC patients could be assessed by nomograms based on different inflammatory indices and clinicopathologic features.展开更多
Objective: To study the effect of α-interferon + gemcitabine combined with infusion chemotherapy on the proliferation and infiltrative growth of advanced bladder cancer. Methods: Patients with advanced bladder cancer...Objective: To study the effect of α-interferon + gemcitabine combined with infusion chemotherapy on the proliferation and infiltrative growth of advanced bladder cancer. Methods: Patients with advanced bladder cancer who accepted bladder infusion chemotherapy in Wuhan Red Cross Hospital between March 2015 and August 2016 were selected and randomly divided into the IFN-α+GEM group and the GEM group who acceptedα-interferon + gemcitabine combined with infusion chemotherapy and single gemcitabine infusion chemotherapy respectively. The contents of bladder cancer markers, cancer cell apoptosis molecules and angiogenesis molecules in urine were detected before treatment and 3 months after treatment. Results: 3 months after treatment, NMP-22, BLCA-4, Apo-A1, HA, CYFRA21-1, ANG, NAC-1, VEGF and bFGF levels in urine of both groups of patients were significantly lower than those before treatment while PTEN, TRAIL, Bim, HSG and p16 levels were significantly higher than those before treatment, and NMP-22, BLCA-4, Apo-A1, HA, CYFRA21-1, ANG, NAC-1, VEGF and bFGF levels in urine of IFN-α+GEM group were significantly lower than those of GEM group while PTEN, TRAIL, Bim, HSG and p16 levels were significantly higher than those of GEM group. Conclusion: α-interferon + gemcitabine combined with infusion chemotherapy can be more effective than single gemcitabine infusion chemotherapy in killing cancer cells and inhibiting the proliferation and infiltrative growth of the cancer cells.展开更多
Background and Aims:To investigate the impact of MR bias field correction on response determination and survival prediction using volumetric tumor enhancement analysis in patients with infiltrative hepatocellular carc...Background and Aims:To investigate the impact of MR bias field correction on response determination and survival prediction using volumetric tumor enhancement analysis in patients with infiltrative hepatocellular carcinoma,after transcatheter arterial chemoembolization(TACE).Methods:This study included 101 patients treated with conventional or drug-eluting beads TACE between the years of 2001 and 2013.Semi-automated 3D quantification software was used to segment and calculate the enhancing tumor volume(ETV)of the liver with and without bias-field correction on multi-phasic contrast-enhanced MRI before and 1-month after initial TACE.ETV(expressed as cm3)at baseline imaging and the relative change in ETV(as%change,ETV%)before and after TACE were used to predict response and survival,respectively.Statistical survival analyses included Kaplan-Meier curve generation and Cox proportional hazards modeling.Q statistics were calculated and used to identify the best cut-off value for ETV to separate responders and non-responders(ETV cm3).The difference in survival was evaluated between responders and non-responders using Kaplan-Meier and Cox models.Results:MR bias field correction correlated with improved response calculation from baseline MR as well as survival after TACE;using a 415 cm3 cut-off for ETV at baseline(hazard ratio:2.00,95%confidence interval:1.23-3.26,p=0.01)resulted in significantly improved response prediction(median survival in patients with baseline ETV<415 cm3:19.66 months vs.≥415 cm3:9.21 months,p<0.001,log-rank test).A≥41%relative decrease in ETV(hazard ratio:0.58,95%confidence interval:0.37-0.93,p=0.02)was significant in predicting survival(ETV≥41%:19.20 months vs.ETV<41%:8.71 months,p=0.008,log-rank test).Without MR bias field correction,response from baseline ETV could be predicted but survival after TACE could not.Conclusions:MR bias field correction improves both response assessment and accuracy of survival prediction using whole liver tumor enhancement analysis from baseline MR after initial TACE in patients with infiltrative hepatocellular carcinoma.展开更多
This study investigated the expression characteristics and clinical significance of gamma-aminobutyric acid A(GABAA)receptor subunit gamma1(GABRG1)in glioma by integrating cancer and normal tissue data from multiple d...This study investigated the expression characteristics and clinical significance of gamma-aminobutyric acid A(GABAA)receptor subunit gamma1(GABRG1)in glioma by integrating cancer and normal tissue data from multiple databases and combining them with experimental evidence.The research revealed that GABRG1 exhibited low expression levels in glioma,and its low expression was closely associated with unfavorable clinical outcomes.Furthermore,a prognostic model with strong decision-making ability was constructed using multivariate Cox regression analysis,incorporating age,isocitric dehydrogenase(IDH)mutation status,O6-methylguanine-DNA methyltransferase(MGMT)methylation status,World Health Organization(WHO)grade,and GABRG1 expression.Additionally,GABRG1 might be associated with the expression of tumor-associated macrophages and was significantly linked to immune regulatory processes.This study provided a new target for immunotherapy in glioma and offered a novel indicator for predicting and evaluating the clinical prognosis of patients.展开更多
Water infiltration in loess is one of the most significant processes that can lead to geological disasters on the Loess Plateau in China.However,the spatiotemporal characteristics of infiltration in intact loess,parti...Water infiltration in loess is one of the most significant processes that can lead to geological disasters on the Loess Plateau in China.However,the spatiotemporal characteristics of infiltration in intact loess,particularly the heterogeneity of three-dimensional(3D)seepage and its relationship with soil properties,remain poorly understood.This study conducted field infiltration tests on a 3 m×3 m loess column,instrumented with 48 moisture sensors to monitor 3D seepage and infiltration rates.Both horizontal and vertical infiltration behaviors were analyzed,alongside a detailed characterization of soil physical properties.The results demonstrated that the water infiltration process was significantly heterogeneous in intact loess,with wetting front velocities varying considerably across profiles and depths,despite relatively uniform physical properties.The infiltration process also exhibited pronounced anisotropy,with vertical wetting front velocities at least 10 times higher than those of the horizontal velocities.The in situ tests indicated that the physical properties were not the primary factors influencing infiltration.However,the microfeatures that facilitated the formation of preferential pathways exerted the most significant influence on the water infiltration process in thick unsaturated loess.Additionally,prior infiltration events negatively impacted subsequent infiltration in thick unsaturated loess.These findings enhance the understanding of loess infiltration dynamics,providing insights into unsaturated flow processes and their implications for geological stability in loess regions.展开更多
The impact mechanism of vegetation on slope soil water infiltration and stability in the loess areas of the northeastern Qinghai-Tibet Plateau remains unclear.Understanding this mechanism is crucial for regional ecolo...The impact mechanism of vegetation on slope soil water infiltration and stability in the loess areas of the northeastern Qinghai-Tibet Plateau remains unclear.Understanding this mechanism is crucial for regional ecological restoration and shallow geological disaster prevention.This study investigated slopes covered by Caragana korshinskii Kom.by employing double-ring infiltration tests to explore the permeability characteristics and influencing factors of root-containing soils and to propose an appropriate infiltration model.Considering the synergistic effects of the canopy and roots,the hydrological response and stability of vegetation-covered slopes under rainfall infiltration conditions were evaluated through numerical simulation analysis.The results revealed that within the main root distribution layer(0-0.5 m),the initial and average infiltration rates and the permeability coefficient of the root-soil composite were significantly higher than those of bare land.Coarse roots with diameters of>5 mm were the key contributors to enhancement of the infiltration capacity.The dry density,fine particle content,and initial water content of the soil around the roots were negatively correlated with the infiltration process.The Horton model effectively reproduced the infiltration process under the canopy and on bare land.The roots significantly accelerated the advance of the slope wetting front during rainfall infiltration,whereas the canopy delayed its onset and progression.The rainfall infiltration process on vegetation-covered slopes was divided into three stages:the equilibrium infiltration stage,optimal infiltration stage beneath the canopy,and secondary equilibrium stage.Vegetation enhances slope stability through coupling of the canopy and root,with an order of canopy-root mode>root mode>bare slope.Under heavy rainfall conditions,the direct contribution of canopy interception to slope stability is limited,and its primary role is to delay the occurrence of instability.During this period,the mechanical effect of roots becomes the dominant mechanism in slope protection.展开更多
Post-kidney transplant rejection is a critical factor influencing transplant success rates and the survival of transplanted organs.With the rapid advancement of artificial intelligence technologies,machine learning(ML...Post-kidney transplant rejection is a critical factor influencing transplant success rates and the survival of transplanted organs.With the rapid advancement of artificial intelligence technologies,machine learning(ML)has emerged as a powerful data analysis tool,widely applied in the prediction,diagnosis,and mechanistic study of kidney transplant rejection.This mini-review systematically summarizes the recent applications of ML techniques in post-kidney transplant rejection,covering areas such as the construction of predictive models,identification of biomarkers,analysis of pathological images,assessment of immune cell infiltration,and formulation of personalized treatment strategies.By integrating multi-omics data and clinical information,ML has significantly enhanced the accuracy of early rejection diagnosis and the capability for prognostic evaluation,driving the development of precision medicine in the field of kidney transplantation.Furthermore,this article discusses the challenges faced in existing research and potential future directions,providing a theoretical basis and technical references for related studies.展开更多
Unmanned combat aerial vehicles require lightweight,stealth-capable exhaust systems.However,traditional metallic nozzles increase radar detectability and reduce range,while advanced composites offer high performance b...Unmanned combat aerial vehicles require lightweight,stealth-capable exhaust systems.However,traditional metallic nozzles increase radar detectability and reduce range,while advanced composites offer high performance but are expensive.Therefore,to improve the operational range and survivability of unmanned combat aerial vehicles,a lightweight,high-temperature-resistant,oxidation-resistant,and low-observable composite exhaust nozzle is developed to replace conventional metallic straight-type nozzles.The nozzle features a double serpentine shape to reduce radar and infrared signatures and is manufactured as a monolithic structure using the filament winding process,accommodating the complex geometry and large size(length:1.8 m,width:0.8 m).The exhaust nozzle consists of a ceramic matrix composite made of silicon carbide fibers and a silicon oxycarbide matrix,which absorbs and scatters radio frequency signals while withstanding prolonged exposure to high-temperature(700℃)oxidizing environments typical of engine exhaust gases.The polysiloxane resin used to produce the silicon oxycarbide matrix poses significant challenges owing to its low tackiness and high viscosity variations depending on the presence of nanoparticles,making filament winding difficult.These challenges are addressed by optimizing resin viscosity and winding pattern design.As a result,the tensile strength of the composite specimens fabricated with the optimized viscosity increases by 228.03% before pyrolysis and 97.68%after pyrolysis,compared with that of the non-optimized specimens.In addition,the density and tensile strength of the composite processed via three cycles of polymer infiltration and pyrolysis increased by 13.08% and 80.37%,respectively,compared to those of the non-densified composite.High-temperature oxidation and flame tests demonstrate exceptional thermal and oxidative stability.Furthermore,when compared with carbon fiber-reinforced ceramic matrix composites,the developed composite exhibits a permittivity at least two levels lower and a reflection loss below7 dB within the frequency range of 9.3-10.9 GHz,underscoring its superior electromagnetic stealth performance.展开更多
Objective:To assess the efficacy of chlorophyl lderivative（CPD4）-Photodynamic therapy（PDT）in preventing postoperative recurrence of the in filtrativecancer of the urinary bladder-Methods:32 patients were treated w...Objective:To assess the efficacy of chlorophyl lderivative（CPD4）-Photodynamic therapy（PDT）in preventing postoperative recurrence of the in filtrativecancer of the urinary bladder-Methods:32 patients were treated with CPD4-PDT postoperationally to prevent therecurrence of can cerall of which being followedup.Results:There currenc erate was42.1%inT2 tumors and 69.2%inT3 tumors（P＜0.05）,and the survival period without tumor has been 19.8±14.8months in T2 tumors,and 22.67±19.72months in T3 tumors（P＞0.05）.There was verysignificant difference inrecurrent rate between grade I and gradeⅡ、Ⅲpatients（0%and66.7%,P<0.001）.ConcIusion:CPD4-PDT is a safe and effectiv emeasureto prevent the recurrence in infiltrative bladder cancer after operation.展开更多
Acute eosinophilic pneumonia(AEP) is a pulmonary condition characterized by acute febrile illness and respiratory distress,with bilateral pulmonary infiltrates,particularly eosinophilic infiltration of the lungs.^([1]...Acute eosinophilic pneumonia(AEP) is a pulmonary condition characterized by acute febrile illness and respiratory distress,with bilateral pulmonary infiltrates,particularly eosinophilic infiltration of the lungs.^([1])Amiodarone,a widely applied antiarrhythmic agent,has been reported as a potential cause of drug-induced AEP.^([2]) Most reported cases of amiodarone-induced AEP typically occur following prolonged exposure for two months or more.展开更多
Objectives:Bladder cancer(BCa)progression is closely linked to the immune microenvironment.However,the key molecules that regulate this microenvironment and their specific mechanisms remain poorly understood.This stud...Objectives:Bladder cancer(BCa)progression is closely linked to the immune microenvironment.However,the key molecules that regulate this microenvironment and their specific mechanisms remain poorly understood.This study aims to identify a key molecule and elucidate its mechanisms,providing a theoretical basis for identifying novel therapeutic targets.Methods:Immune microenvironment-related genes in BCa were identified using The Cancer Genome Atlas and Shanghai Tenth People’s Hospital datasets.Proteasome 26S subunit non-ATPase 2(PSMD2)expression was validated via quantitative polymerase chain reaction(qPCR),Western blot(WB)analysis,and immunofluorescence(IF).In vitro and in vivo experiments confirmed the role of PSMD2 in cell proliferation,invasion,and migration.Kyoto encyclopedia of genes and genomes(KEGG)and Gene Ontology(GO)analyses were conducted to assess PSMD2’s influence on immune microenvironment remodeling.A pathomics model predicted PSMD2 expression in patients with BCa.Results:PSMD2 was identified as a critical factor in BCa,with high expression correlating with poor prognosis and tumor progression.Mechanistically,PSMD2 enhances malignancy by promoting mitogen-activated protein kinase kinase(MEK)and extracellular signal-regulated kinase(ERK)phosphorylation within the mitogen-activated protein kinase(MAPK)signaling pathway.Combined bioinformatics and experimental analyses reveal that PSMD2 downregulates chemokine(C-X-C motif)ligand 14(CXCL14)expression and secretion via the MAPK pathway,thereby remodeling the immune microenvironment and driving tumor progression.Pathomics analysis further supports the potential of PSMD2 expression as a predictive marker in BCa tissues.Conclusion:PSMD2 is overexpressed in BCa and significantly correlates with poor prognosis and tumor progression.It promotes malignant development and immune microenvironment remodeling through the MAPK pathway.Pathological analysis can predict PSMD2 expression,offering valuable insights into immunotherapy responses and survival outcomes.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is one of the most prevalent and aggressive forms of liver cancer,with high morbidity and poor prognosis due to late diagnosis and limited treatment options.Despite advances in ...BACKGROUND Hepatocellular carcinoma(HCC)is one of the most prevalent and aggressive forms of liver cancer,with high morbidity and poor prognosis due to late diagnosis and limited treatment options.Despite advances in understanding its molecular mechanisms,effective biomarkers for early detection and targeted therapy remain scarce.Zinc finger protein 71(ZNF71),a zinc-finger protein,has been implicated in various cancers,yet its role in HCC remains largely unexplored.This gap in knowledge underscores the need for further investigation into the ZNF71 of potential as a diagnostic or therapeutic target in HCC.AIM To explore the expression levels,clinical relevance,and molecular mechanisms of ZNF71 in the progression of HCC.METHODS The study evaluated ZNF71 expression in 235 HCC specimens and 13 noncancerous liver tissue samples using immunohistochemistry.High-throughput datasets were employed to assess the differential expression of ZNF71 in HCC and its association with clinical and pathological features.The impact of ZNF71 on HCC cell line growth was examined through clustered regularly interspaced short palindromic repeat knockout screens.Co-expressed genes were identified and analyzed for enrichment using LinkedOmics and Sangerbox 3.0,focusing on significant correlations(P<0.01,correlation coefficient≥0.3).Furthermore,the relationship between ZNF71 expression and immune cell infiltration was quantified using TIMER2.0.RESULTS ZNF71 showed higher expression in HCC tissues vs non-tumorous tissues,with a significant statistical difference(P<0.05).Data from the UALCAN platform indicated increased ZNF71 levels across early to mid-stage HCC,correlating with disease severity(P<0.05).High-throughput analysis presented a standardized mean difference in ZNF71 expression of 0.55(95%confidence interval[CI]:0.34-0.75).The efficiency of ZNF71 mRNA was evaluated,yielding an area under the curve of 0.78(95%CI:0.75-0.82),a sensitivity of 0.63(95%CI:0.53-0.72),and a specificity of 0.82(95%CI:0.73-0.89).Diagnostic likelihood ratios were positive at 3.61(95%CI:2.41-5.41)and negative at 0.45(95%CI:0.36-0.56).LinkedOmics analysis identified strong positive correlations of ZNF71 with genes such as ZNF470,ZNF256,and ZNF285.Pathway enrichment analyses highlighted associations with herpes simplex virus type 1 infection,the cell cycle,and DNA replication.Negative correlations involved metabolic pathways,peroxisomes,and fatty acid degradation.TIMER2.0 analysis demonstrated positive correlations of high ZNF71 expression with various immune cell types,including CD4^(+)T cells,B cells,regulatory T cells,monocytes,macrophages,and myeloid dendritic cells.CONCLUSION ZNF71 is significantly upregulated in HCC,correlating with the disease’s clinical and pathological stages.It appears to promote HCC progression through mechanisms involving the cell cycle and metabolism and is associated with immune cell infiltration.These findings suggest that ZNF71 could be a novel target for diagnosing and treating HCC.展开更多
Background:Heat shock protein B8(HSPB8)is implicated in autophagy,and its aberrant expression has been linked to both the ini-tiation and progression of tumors.However,the role and function of HSPB8 in colorectal canc...Background:Heat shock protein B8(HSPB8)is implicated in autophagy,and its aberrant expression has been linked to both the ini-tiation and progression of tumors.However,the role and function of HSPB8 in colorectal cancer(CRC)and across multiple cancer types remain unclear.This study aimed to map the transcriptome of autophagy-related genes in CRC and to conduct a pan-cancer analysis of HSPB8 as both a prognostic and immunological biomarker.Methods:We performed bioinformatics analyses on GSE113513 and GSE74602 to identify differentially expressed genes(DEGs)in CRC.These DEGs were then compared with autophagy-related genes to identify critical overlapping genes.The Kaplan-Meier plotter was used to verify the ex-pression of autophagy-linked DEGs and evaluate its prognostic value.The protein expression of Hub gene in CRC was analyzed using the Human Protein Atlas database.The cBioPortal was used to analyze the type and frequency of Hub gene mutations.The TIMER(Tumor Immune Estimation Resource)database was used to study the correlation between HSPB8 and immune infiltration in CRC.Results:In total,825 DEGs were identified,including 8 autophagy-linked DEGs:ATIC,MYC,HSPB8,TNFSF10,BCL2,TP53INP2,ITPR1,and NKX2-3.Survival analysis showed that increased HSPB8 expression significantly correlates with poor prognosis in patients with CRC(p<0.05).HSPB8 was also found to be differentially expressed in various cancer types,correlating with both prognosis and immune infiltration.Further,changes in HSPB8 methylation and phosphorylation status were observed across several cancers,suggesting potential regulatory mechanisms.Therefore,HSPB8 may serve as a crucial prognostic and immunological biomarker in CRC and other cancers.Conclusions:This study provides new insights into the role of autophagy-related genes in cancer progression and highlights HSPB8 as a potential target for cancer diagnostics and therapy.展开更多
To effectively regulate the grain boundary infiltration in CoCrFeMnNi high-entropy alloy(Cantor alloys,HEA)caused by the violent atomic interdiffusion,the higher configuration entropy on Cantor alloys surface was desi...To effectively regulate the grain boundary infiltration in CoCrFeMnNi high-entropy alloy(Cantor alloys,HEA)caused by the violent atomic interdiffusion,the higher configuration entropy on Cantor alloys surface was designed and realized via eutectic high-entropy(EHEA)transformation.Meanwhile,to effectively alleviate the residual stress caused by the notable difference in the thermal expansion coefficient(CTE)between Cantor alloys and Zr-3 alloys,a cladding layer was applied to the HEA surface using laser cladding technology of Nb,followed by brazing to Zr-3 alloys with Zr63.2Cu filler.The cladding layer’s microstructure comprised Nbss and FCC+(Co,Ni)_(2) Nb eutectic structure,resulting from an in-situ reaction between Cantor alloys and Nb.The Nbss and FCC demonstrated good plasticity,and the(Co,Ni)_(2) Nb Laves phase provided increased strength,endowing both good plastic deformation ability and strength of the cladding layer.Notably,the existence of EHEA in the laser cladding layer made the Cantor alloy entropy from 1.61 R to 1.77 R,greatly enhancing its thermal stability and suppressing the grave grain boundary infiltration.Joints produced via laser cladding with Nb-assisted brazing exhibited a complex microstructure(HEA/Nbss+FCC+(Co,Ni)_(2)Nb/(Zr,Nb)(Cr,Mn)_(2)+(Zr,Nb)ss/(Zr,Nb)_(2)(Cu,Ni,Co,Fe)+(Zr,Nb)(Cr,Mn)_(2)+(Zr,Nb)ss/Zr-3) and a significantly improved shear strength of 242.8 MPa at 1010℃ for 10 min,42.4%higher than that of directly brazed joints.This improvement was attributed to reduced grain boundary infiltration,alleviated residual stress due to CTE disparity,and eliminated micro-cracks in the brazing seam.This study presents an effective solution for reducing residual stresses and achieving reliable bonding between Cantor alloys and Zr-3 alloys,with potential applications in brazing CoCrFeNi-based HEA and Zr-3 due to the beneficial eutectic reaction between CoCrFeNi and Nb.展开更多
基金Supported by National Natural Science Foundation of China,No.81871979Natural Science Foundation of Fujian Province,No.2021J02056,No.2021J05276 and No.2020CXB048Medical and Health Sciences Foundation of Xiamen,No.3502Z20199171 and No.3502Z20204002.
文摘BACKGROUND Proteomic signatures of Ming's infiltrative gastric cancer(IGC)remain unknown.AIM To elucidate the molecular characteristics of IGC at the proteomics level.METHODS Twelve pairs of IGC and adjacent normal tissues were collected and their proteomes were analyzed by high performance liquid chromatography tandem mass spectrometry.The identified peptides were sequenced de novo and matched against the SwissProt database using Maxquant software.The differentially expressed proteins(DEPs)were screened using|log2(Fold change)|>1 and P-adj<0.01 as the thresholds.The expression levels of selected proteins were verified by Western blotting.The interaction network of the DEPs was constructed with the STRING database and visualized using Cytoscape with cytoHubba software.The DEPs were functionally annotated using clusterProfiler,STRING and DAVID for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways.P<0.05 was considered statistically significant.RESULTS A total of 7361 DEPs were identified,of which 94 were significantly up-regulated and 223 were significantly down-regulated in IGC relative to normal gastric tissues.The top 10 up-regulated proteins were MRTO4,BOP1,PES1,WDR12,BRIX1,NOP2,POLR1C,NOC2L,MYBBP1A and TSR1,and the top 10 down-regulated proteins were NDUFS8,NDUFS6,NDUFA8,NDUFA5,NDUFC2,NDUFB8,NDUFB5,NDUFB9,UQCRC2 and UQCRC1.The up-regulated proteins were enriched for 9 biological processes including DNA replication,ribosome biogenesis and initiation of DNA replication,and the cellular component MCM complex.Among the down-regulated proteins,17 biological processes were enriched,including glucose metabolism,pyruvic acid metabolism and fatty acidβ-oxidation.In addition,the mitochondrial inner membrane,mitochondrial matrix and mitochondrial proton transport ATP synthase complex were among the 6 enriched cellular components,and 11 molecular functions including reduced nicotinamide adenine dinucleotide dehydrogenase activity,acyl-CoA dehydrogenase activity and nicotinamide adenine dinucleotide binding were also enriched.The significant KEGG pathways for the up-regulated proteins were DNA replication,cell cycle and mismatch repair,whereas 18 pathways including oxidative phosphorylation,fatty acid degradation and phenylalanine metabolism were significantly enriched among the down-regulated proteins.CONCLUSION The proteins involved in cell cycle regulation,DNA replication and mismatch repair,and metabolism were significantly altered in IGC,and the proteomic profile may enable the discovery of novel biomarkers.
基金This project is supported by National Natural Science Foundation of China (No.50075017)Municipal Youth Foundation of Harbin, China(No.2003AFQXJ035).
文摘The effect of deformation of porous material on infiltrative performance is investigated. Based on Darcy theory and Boit principle, the Reynolds equation and mathematical expression of deformable metal rubber （MR） material under laminar flow are obtained according to the change of porosity of metal rubber. It is shown that the throttle of MR material is dependent on its porosity and diameter of metal wires. It will be of great value for the application of MR in throttle field.
文摘OBJECT:Progression of infiltrative low-grade gliomas(LGGs)has been reported previously.The limitations ofsuch studies include diverse histological grading systems,intervening therapy,and the lack of histological confir-mation of malignant tumor progression.The aim of this study was to determine tumor progression in adult patientswith an initial diagnosis of infiltrative LGG who subsequently underwent a repeated operation,but no other inter-vening therapy.The authors examined factors that may be associated with tumor progression.
文摘PURPOSE:This study was conducted to investigate the incidence of ERBB1 amplification and overexpression in samples of diffusely infiltrative (WHO grades Ⅱ-Ⅳ) pediatric brain stem glioma (BSG) and determine the relationship of these abnormalities to expression and mutation of TP53 and tumor grade. Experimental Design: After central pathology review, the incidence of ERBB1 amplification and overexpression was determined in 28 samples (18 surgical biopsy and 10 postmortem specimens) of BSG using quantitative PCR and immunohistochemistry,
基金Supported by the Harbin Science and Technology Bureau Research and Development Project of Applied Technology,No. 2017RAXXJ054Nn 10 Program of Harbin Medical University Cancer Hospital,No. Nn 10 PY 2017-03
文摘BACKGROUND Inflammatory indices are considered to be potential prognostic biomarkers for patients with gastric cancer(GC).However,there is no evidence defining the prognostic significance of inflammatory indices for GC with different tumor infiltrative pattern(INF)types.AIM To evaluate the significance of inflammatory indices and INF types in predicting the prognosis of patients with GC.METHODS A total of 962 patients who underwent radical gastrectomy were retrospectively selected for this study.Patients were categorized into the expansive growth type(INFa),the intermediate type(INFb),and the infiltrative growth type(INFc)groups.The cutoff values of inflammatory indices were analyzed by receiver operating characteristic curves.The Kaplan–Meier method and log-rank test were used to analyze overall survival(OS).The chi-square test was used to analyze the association between inflammatory indices and clinical characteristics.The independent risk factors for prognosis in each group were analyzed by univariate and multivariate analyses based on logistic regression.Nomogram models were constructed by R studio.RESULTS The INFc group had the worst OS(P<0.001).The systemic immune-inflammation index(P=0.039)and metastatic lymph node ratio(mLNR)(P=0.003)were independent risk factors for prognosis in the INFa group.The platelet-lymphocyte ratio(PLR)(P=0.018),age(P=0.026),body mass index(P=0.003),and postsurgical tumor node metastasis(pTNM)stage(P<0.001)were independent risk factors for prognosis in the INFb group.The PLR(P=0.021),pTNM stage(P=0.028),age(P=0.021),and mLNR(P=0.002)were independent risk factors for prognosis in the INFc group.The area under the curve of the nomogram model for predicting 5-year survival in the INFa group,INFb group,and INFc group was 0.787,0.823,and 0.781,respectively.CONCLUSION The outcome of different INF types GC patients could be assessed by nomograms based on different inflammatory indices and clinicopathologic features.
文摘Objective: To study the effect of α-interferon + gemcitabine combined with infusion chemotherapy on the proliferation and infiltrative growth of advanced bladder cancer. Methods: Patients with advanced bladder cancer who accepted bladder infusion chemotherapy in Wuhan Red Cross Hospital between March 2015 and August 2016 were selected and randomly divided into the IFN-α+GEM group and the GEM group who acceptedα-interferon + gemcitabine combined with infusion chemotherapy and single gemcitabine infusion chemotherapy respectively. The contents of bladder cancer markers, cancer cell apoptosis molecules and angiogenesis molecules in urine were detected before treatment and 3 months after treatment. Results: 3 months after treatment, NMP-22, BLCA-4, Apo-A1, HA, CYFRA21-1, ANG, NAC-1, VEGF and bFGF levels in urine of both groups of patients were significantly lower than those before treatment while PTEN, TRAIL, Bim, HSG and p16 levels were significantly higher than those before treatment, and NMP-22, BLCA-4, Apo-A1, HA, CYFRA21-1, ANG, NAC-1, VEGF and bFGF levels in urine of IFN-α+GEM group were significantly lower than those of GEM group while PTEN, TRAIL, Bim, HSG and p16 levels were significantly higher than those of GEM group. Conclusion: α-interferon + gemcitabine combined with infusion chemotherapy can be more effective than single gemcitabine infusion chemotherapy in killing cancer cells and inhibiting the proliferation and infiltrative growth of the cancer cells.
文摘Background and Aims:To investigate the impact of MR bias field correction on response determination and survival prediction using volumetric tumor enhancement analysis in patients with infiltrative hepatocellular carcinoma,after transcatheter arterial chemoembolization(TACE).Methods:This study included 101 patients treated with conventional or drug-eluting beads TACE between the years of 2001 and 2013.Semi-automated 3D quantification software was used to segment and calculate the enhancing tumor volume(ETV)of the liver with and without bias-field correction on multi-phasic contrast-enhanced MRI before and 1-month after initial TACE.ETV(expressed as cm3)at baseline imaging and the relative change in ETV(as%change,ETV%)before and after TACE were used to predict response and survival,respectively.Statistical survival analyses included Kaplan-Meier curve generation and Cox proportional hazards modeling.Q statistics were calculated and used to identify the best cut-off value for ETV to separate responders and non-responders(ETV cm3).The difference in survival was evaluated between responders and non-responders using Kaplan-Meier and Cox models.Results:MR bias field correction correlated with improved response calculation from baseline MR as well as survival after TACE;using a 415 cm3 cut-off for ETV at baseline(hazard ratio:2.00,95%confidence interval:1.23-3.26,p=0.01)resulted in significantly improved response prediction(median survival in patients with baseline ETV<415 cm3:19.66 months vs.≥415 cm3:9.21 months,p<0.001,log-rank test).A≥41%relative decrease in ETV(hazard ratio:0.58,95%confidence interval:0.37-0.93,p=0.02)was significant in predicting survival(ETV≥41%:19.20 months vs.ETV<41%:8.71 months,p=0.008,log-rank test).Without MR bias field correction,response from baseline ETV could be predicted but survival after TACE could not.Conclusions:MR bias field correction improves both response assessment and accuracy of survival prediction using whole liver tumor enhancement analysis from baseline MR after initial TACE in patients with infiltrative hepatocellular carcinoma.
基金Supported by the National Natural Science Foundation of China(82271340,82071368)the Outstanding Youth Funding of Harbin Medical University(HYD2020JQ0016)the Horizontal Subject(86010900)。
文摘This study investigated the expression characteristics and clinical significance of gamma-aminobutyric acid A(GABAA)receptor subunit gamma1(GABRG1)in glioma by integrating cancer and normal tissue data from multiple databases and combining them with experimental evidence.The research revealed that GABRG1 exhibited low expression levels in glioma,and its low expression was closely associated with unfavorable clinical outcomes.Furthermore,a prognostic model with strong decision-making ability was constructed using multivariate Cox regression analysis,incorporating age,isocitric dehydrogenase(IDH)mutation status,O6-methylguanine-DNA methyltransferase(MGMT)methylation status,World Health Organization(WHO)grade,and GABRG1 expression.Additionally,GABRG1 might be associated with the expression of tumor-associated macrophages and was significantly linked to immune regulatory processes.This study provided a new target for immunotherapy in glioma and offered a novel indicator for predicting and evaluating the clinical prognosis of patients.
基金supported by the National Natural Science Foundation of China(Grant No.42372307)the Natural Science Basic Research Program of Shaanxi Province(Grant No.2020JC-07)the SCEGC-XJTU Joint Research Center for Future City Construction and Management Innovation,Shaanxi Provincial Land Engineering Construction Group,and Xi’an Jiaotong University(Grant No.20221220).
文摘Water infiltration in loess is one of the most significant processes that can lead to geological disasters on the Loess Plateau in China.However,the spatiotemporal characteristics of infiltration in intact loess,particularly the heterogeneity of three-dimensional(3D)seepage and its relationship with soil properties,remain poorly understood.This study conducted field infiltration tests on a 3 m×3 m loess column,instrumented with 48 moisture sensors to monitor 3D seepage and infiltration rates.Both horizontal and vertical infiltration behaviors were analyzed,alongside a detailed characterization of soil physical properties.The results demonstrated that the water infiltration process was significantly heterogeneous in intact loess,with wetting front velocities varying considerably across profiles and depths,despite relatively uniform physical properties.The infiltration process also exhibited pronounced anisotropy,with vertical wetting front velocities at least 10 times higher than those of the horizontal velocities.The in situ tests indicated that the physical properties were not the primary factors influencing infiltration.However,the microfeatures that facilitated the formation of preferential pathways exerted the most significant influence on the water infiltration process in thick unsaturated loess.Additionally,prior infiltration events negatively impacted subsequent infiltration in thick unsaturated loess.These findings enhance the understanding of loess infiltration dynamics,providing insights into unsaturated flow processes and their implications for geological stability in loess regions.
基金funded by Science and Technology Program of Qinghai Province of China(2024-SF-129)the National Natural Science Foundation of China(42002283).
文摘The impact mechanism of vegetation on slope soil water infiltration and stability in the loess areas of the northeastern Qinghai-Tibet Plateau remains unclear.Understanding this mechanism is crucial for regional ecological restoration and shallow geological disaster prevention.This study investigated slopes covered by Caragana korshinskii Kom.by employing double-ring infiltration tests to explore the permeability characteristics and influencing factors of root-containing soils and to propose an appropriate infiltration model.Considering the synergistic effects of the canopy and roots,the hydrological response and stability of vegetation-covered slopes under rainfall infiltration conditions were evaluated through numerical simulation analysis.The results revealed that within the main root distribution layer(0-0.5 m),the initial and average infiltration rates and the permeability coefficient of the root-soil composite were significantly higher than those of bare land.Coarse roots with diameters of>5 mm were the key contributors to enhancement of the infiltration capacity.The dry density,fine particle content,and initial water content of the soil around the roots were negatively correlated with the infiltration process.The Horton model effectively reproduced the infiltration process under the canopy and on bare land.The roots significantly accelerated the advance of the slope wetting front during rainfall infiltration,whereas the canopy delayed its onset and progression.The rainfall infiltration process on vegetation-covered slopes was divided into three stages:the equilibrium infiltration stage,optimal infiltration stage beneath the canopy,and secondary equilibrium stage.Vegetation enhances slope stability through coupling of the canopy and root,with an order of canopy-root mode>root mode>bare slope.Under heavy rainfall conditions,the direct contribution of canopy interception to slope stability is limited,and its primary role is to delay the occurrence of instability.During this period,the mechanical effect of roots becomes the dominant mechanism in slope protection.
文摘Post-kidney transplant rejection is a critical factor influencing transplant success rates and the survival of transplanted organs.With the rapid advancement of artificial intelligence technologies,machine learning(ML)has emerged as a powerful data analysis tool,widely applied in the prediction,diagnosis,and mechanistic study of kidney transplant rejection.This mini-review systematically summarizes the recent applications of ML techniques in post-kidney transplant rejection,covering areas such as the construction of predictive models,identification of biomarkers,analysis of pathological images,assessment of immune cell infiltration,and formulation of personalized treatment strategies.By integrating multi-omics data and clinical information,ML has significantly enhanced the accuracy of early rejection diagnosis and the capability for prognostic evaluation,driving the development of precision medicine in the field of kidney transplantation.Furthermore,this article discusses the challenges faced in existing research and potential future directions,providing a theoretical basis and technical references for related studies.
基金supported by the Agency for Defense Development Grant Funded by the Korean Government(Grant No.912822501).
文摘Unmanned combat aerial vehicles require lightweight,stealth-capable exhaust systems.However,traditional metallic nozzles increase radar detectability and reduce range,while advanced composites offer high performance but are expensive.Therefore,to improve the operational range and survivability of unmanned combat aerial vehicles,a lightweight,high-temperature-resistant,oxidation-resistant,and low-observable composite exhaust nozzle is developed to replace conventional metallic straight-type nozzles.The nozzle features a double serpentine shape to reduce radar and infrared signatures and is manufactured as a monolithic structure using the filament winding process,accommodating the complex geometry and large size(length:1.8 m,width:0.8 m).The exhaust nozzle consists of a ceramic matrix composite made of silicon carbide fibers and a silicon oxycarbide matrix,which absorbs and scatters radio frequency signals while withstanding prolonged exposure to high-temperature(700℃)oxidizing environments typical of engine exhaust gases.The polysiloxane resin used to produce the silicon oxycarbide matrix poses significant challenges owing to its low tackiness and high viscosity variations depending on the presence of nanoparticles,making filament winding difficult.These challenges are addressed by optimizing resin viscosity and winding pattern design.As a result,the tensile strength of the composite specimens fabricated with the optimized viscosity increases by 228.03% before pyrolysis and 97.68%after pyrolysis,compared with that of the non-optimized specimens.In addition,the density and tensile strength of the composite processed via three cycles of polymer infiltration and pyrolysis increased by 13.08% and 80.37%,respectively,compared to those of the non-densified composite.High-temperature oxidation and flame tests demonstrate exceptional thermal and oxidative stability.Furthermore,when compared with carbon fiber-reinforced ceramic matrix composites,the developed composite exhibits a permittivity at least two levels lower and a reflection loss below7 dB within the frequency range of 9.3-10.9 GHz,underscoring its superior electromagnetic stealth performance.
文摘Objective:To assess the efficacy of chlorophyl lderivative（CPD4）-Photodynamic therapy（PDT）in preventing postoperative recurrence of the in filtrativecancer of the urinary bladder-Methods:32 patients were treated with CPD4-PDT postoperationally to prevent therecurrence of can cerall of which being followedup.Results:There currenc erate was42.1%inT2 tumors and 69.2%inT3 tumors（P＜0.05）,and the survival period without tumor has been 19.8±14.8months in T2 tumors,and 22.67±19.72months in T3 tumors（P＞0.05）.There was verysignificant difference inrecurrent rate between grade I and gradeⅡ、Ⅲpatients（0%and66.7%,P<0.001）.ConcIusion:CPD4-PDT is a safe and effectiv emeasureto prevent the recurrence in infiltrative bladder cancer after operation.
基金supported by the Anhui Provincial Health and Medical Research Project (AHWJ2023A30277)。
文摘Acute eosinophilic pneumonia(AEP) is a pulmonary condition characterized by acute febrile illness and respiratory distress,with bilateral pulmonary infiltrates,particularly eosinophilic infiltration of the lungs.^([1])Amiodarone,a widely applied antiarrhythmic agent,has been reported as a potential cause of drug-induced AEP.^([2]) Most reported cases of amiodarone-induced AEP typically occur following prolonged exposure for two months or more.
基金supported by the National Natural Science Foundation of China Commission,Youth Project(No.82203150,No.82302304)Anhui Health Commission Research Project(No.2024Aa30184)+7 种基金The Bengbu City Health and Medical Research Project(BBWK2024A103)Cultivation grant for clinical and basic integration research of Shanghai Tenth People’s Hospital(SYYYRH2025020)Doctoral Workstation Foundation of Guangdong Second Provincial General Hospital,China(Grant No.2022BSGZ011)Elevate Engineering Foundation of Guangdong Second Provincial General Hospital,China(Grant No.TJGC2022009)Science and Technology Program of Guangzhou,China(2024A04J4159)China Postdoctoral Science Foundation(2021M702137)Natural Science Foundation of Chongqing(cstc2021jcyj-msxmX1176)Chongming District Sustainable Development Science and Technology Innovation Initiative Project(CKY2022-30).
文摘Objectives:Bladder cancer(BCa)progression is closely linked to the immune microenvironment.However,the key molecules that regulate this microenvironment and their specific mechanisms remain poorly understood.This study aims to identify a key molecule and elucidate its mechanisms,providing a theoretical basis for identifying novel therapeutic targets.Methods:Immune microenvironment-related genes in BCa were identified using The Cancer Genome Atlas and Shanghai Tenth People’s Hospital datasets.Proteasome 26S subunit non-ATPase 2(PSMD2)expression was validated via quantitative polymerase chain reaction(qPCR),Western blot(WB)analysis,and immunofluorescence(IF).In vitro and in vivo experiments confirmed the role of PSMD2 in cell proliferation,invasion,and migration.Kyoto encyclopedia of genes and genomes(KEGG)and Gene Ontology(GO)analyses were conducted to assess PSMD2’s influence on immune microenvironment remodeling.A pathomics model predicted PSMD2 expression in patients with BCa.Results:PSMD2 was identified as a critical factor in BCa,with high expression correlating with poor prognosis and tumor progression.Mechanistically,PSMD2 enhances malignancy by promoting mitogen-activated protein kinase kinase(MEK)and extracellular signal-regulated kinase(ERK)phosphorylation within the mitogen-activated protein kinase(MAPK)signaling pathway.Combined bioinformatics and experimental analyses reveal that PSMD2 downregulates chemokine(C-X-C motif)ligand 14(CXCL14)expression and secretion via the MAPK pathway,thereby remodeling the immune microenvironment and driving tumor progression.Pathomics analysis further supports the potential of PSMD2 expression as a predictive marker in BCa tissues.Conclusion:PSMD2 is overexpressed in BCa and significantly correlates with poor prognosis and tumor progression.It promotes malignant development and immune microenvironment remodeling through the MAPK pathway.Pathological analysis can predict PSMD2 expression,offering valuable insights into immunotherapy responses and survival outcomes.
基金Supported by Joint Project on Regional High Incidence Diseases Research of Guangxi Natural Science Foundation,No.2024GXNSFAA010057 and No.2024GXNSFAA010085Natural Science Foundation of Guangxi,China,No.2022GXNSFBA035657+2 种基金Guangxi Zhuang Autonomous Region Health Commission Self-Financed Scientific Research Project,No.Z20210764Guangxi Zhuang Autonomous Region Administration of Traditional Chinese Medicine Scientific Research Project,No.GXZYA20230270 and No.GXZYA20240305Advanced Innovation Teams and Xinghu Scholars Program of Guangxi Medical University(2022).
文摘BACKGROUND Hepatocellular carcinoma(HCC)is one of the most prevalent and aggressive forms of liver cancer,with high morbidity and poor prognosis due to late diagnosis and limited treatment options.Despite advances in understanding its molecular mechanisms,effective biomarkers for early detection and targeted therapy remain scarce.Zinc finger protein 71(ZNF71),a zinc-finger protein,has been implicated in various cancers,yet its role in HCC remains largely unexplored.This gap in knowledge underscores the need for further investigation into the ZNF71 of potential as a diagnostic or therapeutic target in HCC.AIM To explore the expression levels,clinical relevance,and molecular mechanisms of ZNF71 in the progression of HCC.METHODS The study evaluated ZNF71 expression in 235 HCC specimens and 13 noncancerous liver tissue samples using immunohistochemistry.High-throughput datasets were employed to assess the differential expression of ZNF71 in HCC and its association with clinical and pathological features.The impact of ZNF71 on HCC cell line growth was examined through clustered regularly interspaced short palindromic repeat knockout screens.Co-expressed genes were identified and analyzed for enrichment using LinkedOmics and Sangerbox 3.0,focusing on significant correlations(P<0.01,correlation coefficient≥0.3).Furthermore,the relationship between ZNF71 expression and immune cell infiltration was quantified using TIMER2.0.RESULTS ZNF71 showed higher expression in HCC tissues vs non-tumorous tissues,with a significant statistical difference(P<0.05).Data from the UALCAN platform indicated increased ZNF71 levels across early to mid-stage HCC,correlating with disease severity(P<0.05).High-throughput analysis presented a standardized mean difference in ZNF71 expression of 0.55(95%confidence interval[CI]:0.34-0.75).The efficiency of ZNF71 mRNA was evaluated,yielding an area under the curve of 0.78(95%CI:0.75-0.82),a sensitivity of 0.63(95%CI:0.53-0.72),and a specificity of 0.82(95%CI:0.73-0.89).Diagnostic likelihood ratios were positive at 3.61(95%CI:2.41-5.41)and negative at 0.45(95%CI:0.36-0.56).LinkedOmics analysis identified strong positive correlations of ZNF71 with genes such as ZNF470,ZNF256,and ZNF285.Pathway enrichment analyses highlighted associations with herpes simplex virus type 1 infection,the cell cycle,and DNA replication.Negative correlations involved metabolic pathways,peroxisomes,and fatty acid degradation.TIMER2.0 analysis demonstrated positive correlations of high ZNF71 expression with various immune cell types,including CD4^(+)T cells,B cells,regulatory T cells,monocytes,macrophages,and myeloid dendritic cells.CONCLUSION ZNF71 is significantly upregulated in HCC,correlating with the disease’s clinical and pathological stages.It appears to promote HCC progression through mechanisms involving the cell cycle and metabolism and is associated with immune cell infiltration.These findings suggest that ZNF71 could be a novel target for diagnosing and treating HCC.
基金supported by the NationalNatural Science Foundation of China(no.32360888)the Jiangxi Students’Platform for Innovation and Entrepreneurship Training Program(no.202411843023).
文摘Background:Heat shock protein B8(HSPB8)is implicated in autophagy,and its aberrant expression has been linked to both the ini-tiation and progression of tumors.However,the role and function of HSPB8 in colorectal cancer(CRC)and across multiple cancer types remain unclear.This study aimed to map the transcriptome of autophagy-related genes in CRC and to conduct a pan-cancer analysis of HSPB8 as both a prognostic and immunological biomarker.Methods:We performed bioinformatics analyses on GSE113513 and GSE74602 to identify differentially expressed genes(DEGs)in CRC.These DEGs were then compared with autophagy-related genes to identify critical overlapping genes.The Kaplan-Meier plotter was used to verify the ex-pression of autophagy-linked DEGs and evaluate its prognostic value.The protein expression of Hub gene in CRC was analyzed using the Human Protein Atlas database.The cBioPortal was used to analyze the type and frequency of Hub gene mutations.The TIMER(Tumor Immune Estimation Resource)database was used to study the correlation between HSPB8 and immune infiltration in CRC.Results:In total,825 DEGs were identified,including 8 autophagy-linked DEGs:ATIC,MYC,HSPB8,TNFSF10,BCL2,TP53INP2,ITPR1,and NKX2-3.Survival analysis showed that increased HSPB8 expression significantly correlates with poor prognosis in patients with CRC(p<0.05).HSPB8 was also found to be differentially expressed in various cancer types,correlating with both prognosis and immune infiltration.Further,changes in HSPB8 methylation and phosphorylation status were observed across several cancers,suggesting potential regulatory mechanisms.Therefore,HSPB8 may serve as a crucial prognostic and immunological biomarker in CRC and other cancers.Conclusions:This study provides new insights into the role of autophagy-related genes in cancer progression and highlights HSPB8 as a potential target for cancer diagnostics and therapy.
基金supported by the National Natural Science Foundation of China(Grant Nos.52275321 and 52205348)the Shandong Natural Science Foundation(Grant No.ZR2023JQ021)+3 种基金the Taishan Scholars Foundation of Shandong Province(No.tsqn 201812128)the Innovation Scientists and Technicians Troop Projects of Henan Province(No.204200510031)the Heilongjiang Touyan Innovation Team Program(No.HITTY-20190013)supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIP)(Nos.NRF-2021R1A2C3006662 and NRF-2022R1A5A1030054).
文摘To effectively regulate the grain boundary infiltration in CoCrFeMnNi high-entropy alloy(Cantor alloys,HEA)caused by the violent atomic interdiffusion,the higher configuration entropy on Cantor alloys surface was designed and realized via eutectic high-entropy(EHEA)transformation.Meanwhile,to effectively alleviate the residual stress caused by the notable difference in the thermal expansion coefficient(CTE)between Cantor alloys and Zr-3 alloys,a cladding layer was applied to the HEA surface using laser cladding technology of Nb,followed by brazing to Zr-3 alloys with Zr63.2Cu filler.The cladding layer’s microstructure comprised Nbss and FCC+(Co,Ni)_(2) Nb eutectic structure,resulting from an in-situ reaction between Cantor alloys and Nb.The Nbss and FCC demonstrated good plasticity,and the(Co,Ni)_(2) Nb Laves phase provided increased strength,endowing both good plastic deformation ability and strength of the cladding layer.Notably,the existence of EHEA in the laser cladding layer made the Cantor alloy entropy from 1.61 R to 1.77 R,greatly enhancing its thermal stability and suppressing the grave grain boundary infiltration.Joints produced via laser cladding with Nb-assisted brazing exhibited a complex microstructure(HEA/Nbss+FCC+(Co,Ni)_(2)Nb/(Zr,Nb)(Cr,Mn)_(2)+(Zr,Nb)ss/(Zr,Nb)_(2)(Cu,Ni,Co,Fe)+(Zr,Nb)(Cr,Mn)_(2)+(Zr,Nb)ss/Zr-3) and a significantly improved shear strength of 242.8 MPa at 1010℃ for 10 min,42.4%higher than that of directly brazed joints.This improvement was attributed to reduced grain boundary infiltration,alleviated residual stress due to CTE disparity,and eliminated micro-cracks in the brazing seam.This study presents an effective solution for reducing residual stresses and achieving reliable bonding between Cantor alloys and Zr-3 alloys,with potential applications in brazing CoCrFeNi-based HEA and Zr-3 due to the beneficial eutectic reaction between CoCrFeNi and Nb.
