VEXAS(vacuoles,E1 enzyme,X-linked,autoinflammatory,somatic)syndrome is a severe and progressive disease,characterized by clinical features that bridge rheumatologic and hematologic conditions.[1]VEXAS syndrome is a ra...VEXAS(vacuoles,E1 enzyme,X-linked,autoinflammatory,somatic)syndrome is a severe and progressive disease,characterized by clinical features that bridge rheumatologic and hematologic conditions.[1]VEXAS syndrome is a rare condition that was not reported until 2020.[2]Since then,interest among dermatologists,hematologists,and rheumatologists with published works has increased,[3]but none of them reported in the emergency setting,nor have any cases arisen following COVID-19 infection.展开更多
This work presents the results of investigations to develop and implement methods to effectively collect and purify infiltrates from heaps, situated in the region of Alwernia near Cracow, where more than 3 million ton...This work presents the results of investigations to develop and implement methods to effectively collect and purify infiltrates from heaps, situated in the region of Alwernia near Cracow, where more than 3 million tonnes of waste material resulting from the production of chromium compounds have been stored. It describes a system for the protection of groundwater from these infiltrates which contain 50-400 g m-3 Cr6+, as well as the effectiveness of cheap and simple chemical methods to purify these chromic wastewaters. The infiltrate collection system and the most effective method to decrease the concentration of Cr6+ to a level below 0.1 ppm, as required by Polish and European Union regulations, were implemented in the Alwernia Chemical Works S. A. in the years 1998-1999.展开更多
Enhancer of zeste homolog 2(EZH2)is the catalytic subunit of polycomb repressive complex 2(PRC2).Dysregulation of EZH2 causes alteration of gene expression and functions,thereby promoting cancer development.Recent stu...Enhancer of zeste homolog 2(EZH2)is the catalytic subunit of polycomb repressive complex 2(PRC2).Dysregulation of EZH2 causes alteration of gene expression and functions,thereby promoting cancer development.Recent studies suggest that EZH2 has a potential prognostic role in patients with nonsmall cell lung cancer(NSCLC).However,the prognostic value of EZH2 expression levels in NSCLC is controversial.In this study,we evaluated the prognostic value in lung cancer(LC-LUAD/LUSC)based on data from The Cancer Genome Atlas(TCGA)database.Kruskal-Wallis test,Wilcoxon signed-rank test,and logistic regression were used to evaluate the relationship between EZH2 expression and clinicopathological features.Cox regression and the Kaplan-Meier method were adopted to evaluate prognosis-related factors.Gene set enrichment analysis(GSEA)was performed to identify the key pathways related to EZH2.The correlations between EZH2 and cancer immune infiltrates were investigated by single-sample Gene Set Enrichment Analysis(ssGSEA).EZH2 was found to be up regulated with amplification in tumor tissues in multiple LC cohorts.High EZH2 expression was associated with poorer overall survival(OS).GSEA suggested that EZH2 regulates innate immune system,ECM affiliated,matrisome,surfactant metabolism.Notably,ssGSEA indicated that EZH2 expression was positively correlated with infiltrating levels of Th2 cells and significantly negatively correlated with mast cell infiltration level.These results suggest that EZH2 is associated with LC immune infiltration and significantly over-expressed in lung cancer,and its diagnostic value is better than prognosis,which lays a foundation for further study of the immunomodulatory role of EZH2 in LC.展开更多
Background: The protein encoded by ring finger protein 157 (RNF157) is known to function as an E3 ubiquitinligase. However, whether the level of RNF157 expression in breast cancer correlates with prognosis and immune ...Background: The protein encoded by ring finger protein 157 (RNF157) is known to function as an E3 ubiquitinligase. However, whether the level of RNF157 expression in breast cancer correlates with prognosis and immune cellinfiltration among breast cancer patients remains to be further explored. Methods: In this study, publicly availabledatasets were used for evaluating RNF157 expression in different tumors compared with normal samples. Severalindependent datasets were screened for investigating the relationship between RNF157 and breast cancer survival,different mutation profiles, and tumor immune cell infiltration. We conducted a pathway enrichment analysis toidentify signaling pathways associated with RNF157. Results: Analysis of public and online databases revealed thatRNF157 expression markedly decreased in breast cancer tissue samples compared to non-carcinoma counterparts.Consistently, immunohistochemistry assays also demonstrated this RNF157 down-regulation in breast cancer samples.RNF157 up-regulation could predict the improved survival of breast cancer cases. Further, different RNF157expression level groups exhibited different mutational profiles. Pathway enrichment profiling of RNF157-related genessuggested its possible involvement in regulating breast cancer via the mitogen-activated protein kinase (MAPK)pathway. RNA sequencing (RNA-seq) data and genomic enrichment analysis showed that RNF157 downregulatedseveral genes positively associated with the MAPK signaling pathway. We also explored RNF157 expression andimmune cell infiltration in breast cancer and found that RNF157 mRNA levels were negatively related to non-Timmune cell infiltration. Conclusion: According to our work, RNF157 may be a promising diagnostic biomarker andtherapeutic target for breast cancer.展开更多
Background:Lung cancer,particularly lung adenocarcinoma(LUAD),is highly lethal.Understanding the critical interaction between epithelial-mesenchymal transition(EMT)and the immune status of patients is imperative for c...Background:Lung cancer,particularly lung adenocarcinoma(LUAD),is highly lethal.Understanding the critical interaction between epithelial-mesenchymal transition(EMT)and the immune status of patients is imperative for clinical assessment.Methods:We conducted bioinformatics analysis to identify potential immune-related EMT(iEMT)prognostic genes and explored the immune status in LUAD.Using data from The CancerGenome Atlas andGSE68465,differentially expressed genes,were identified,and a risk modelwas constructed.Cluster analysis was conducted using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways.Results:Our findings revealed 69 differentially expressed iEMT genes,with risk values demonstrating independent prognostic significance for both The Cancer Genome Atlas and GSE68465 samples.The risk value was positively correlated with tumor stage.Immune cell infiltration analysis showed a significant decrease in resting dendritic cells and an increase in CD4 memory T cells in high-risk groups with poor survival prognoses.The immunotherapy analysis revealed weak immunotherapeutic effects in the high-risk group.Conclusions:This study provides insights into potential aberrant differential iEMT genes and risk models and explores immune landscapes that inform personalized immunotherapy in patients with LUAD.展开更多
Background:Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-related deaths globally.Splicing factor proline and glutamine-rich(SFPQ)is a multifunctional protein that controls various biological funct...Background:Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-related deaths globally.Splicing factor proline and glutamine-rich(SFPQ)is a multifunctional protein that controls various biological functions.As a potential therapeutic target and a promising prognostic indicator,the potential effects and processes of SFPQ in HCC require further investigation.Methods:The RNA sequencing data were obtained from the Gene Expression Omnibus,International Cancer Genome Consortium,and The Cancer Genome Atlas databases to analyze SFPQ expression and differentially expressed genes(DEGs).We utilized the LinkedOmics database to identify co-expressed genes.A Venn diagram was constructed to determine the overlapping genes between the DEGs and the co-expressed genes.Functional enrichment analysis was performed on the overlapping genes and DEGs.Furthermore,our study involved functional enrichment analysis,a protein-protein interaction network analysis,and an analysis of immune cell infiltration.The cBioPortal and Tumor Immune Single-cell Hub were utilized to investigate the genetic alterations of SFPQ and the single-cell transcriptome visualization of the tumor microenvironment.A ceRNA network was established with the assistance of the ENCORI website.Finally,we elucidated the clinical significance of SFPQ in HCC by employing Kaplan-Meier survival analysis,univariate and multivariate Cox regression,and prognostic nomogram models.Results:The expression of SFPQ in HCC tissues was significantly elevated compared to normal tissues.GSEA results indicated that increased expression of SFPQ was associated with pathways related to HCC.The ceRNA network,including SFPQ,hsa-miR-101-3p,AC023043.4,AC124798.1,AC145207.5,and GSEC,was constructed with the assistance of ENCORI.High SFPQ expression was related to a poor prognosis in HCC and its subtypes.Univariate and multivariate Cox regression analysis showed that elevated SFPQ expression is an independent predictive factor.Conclusions:The overexpression of SFPQ may serve as a potential prognostic biomarker,indicating a poor prognosis in HCC.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
Background:Hepatocellular carcinoma(HCC)is a leading cause of cancer-related death worldwide.The development of biomarkers for early detection and monitoring of HCC has not shown significant prog-ress.Meanwhile,the se...Background:Hepatocellular carcinoma(HCC)is a leading cause of cancer-related death worldwide.The development of biomarkers for early detection and monitoring of HCC has not shown significant prog-ress.Meanwhile,the second adenomatous polyposis-related gene,MUTYH,which encodes a DNA gly-cosylase,has been observed in its contribution to oxidative DNA damage repair.Abnormal expression of MUTYH can reduce cell survival rate.Therefore,this study investigated the usefulness of MUTYH in diagnosing and prognosis HCC.Materials and methods:Using The Cancer Genome Atlas(TCGA)data,we analyzed the prognostic value of MUTYH in HCC.We used logistic regression,Wilcoxon signed-rank test,and KruskaleWallis test to examine MUTYH expression concerning clinical-pathologic characteristics.Univariate and multivariate Cox regression methods and Kaplan-Meier analysis were applied to determine the related prognostic factors of HCC.The enrichment analysis(GSEA)was used to determine the critical pathways associated with MUTYH.The single-sample gene set enrichment analysis(ssGSEA)was conducted to examine the correlation between MUTYH expression and cancer immune infiltration.Results:The higher expression of MUTYH in HCC patients was associated with a poorer overall survival rate and a shorter disease-specific survival rate.The Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis showed that all differentially expressed genes(DEGs)between the high and low expression levels of MUTYH significantly enriched in the trace ligand-receptor interaction,cell cycle,oocyte meiosis,gap junction,and DNA replication.Group analysis revealed the signals of their open access.The neuron system,M phase,DNA repair,Rho GTPase effector,and cell cycle checkpoints were significantly enriched.ssGSEA showed a positive correlation between MUTYH expression and the infiltration levels of Th2 cells,NK cells,and T helper cells.Moreover,a negative correlation was found between MUTYH expression and the infiltration levels of dendritic cells(DCs)and cytotoxic cells.Conclusions:MUTYH expression levels were positively correlated with immune checkpoint gene expression levels in HCC tissues.The expression level of MUTYH was related to the prognosis of HCC and the immune infiltration of HCC.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
Paraffin-embedded tissue of skin biopsy specimens taken retrospectively from 24 patients with cutaneous malignant lymphomas (CML) and 8 patients with cutaneous lymphoid infiltrates (CLI) and other dennatoses were stud...Paraffin-embedded tissue of skin biopsy specimens taken retrospectively from 24 patients with cutaneous malignant lymphomas (CML) and 8 patients with cutaneous lymphoid infiltrates (CLI) and other dennatoses were studied retrospectively with PCIO immunostaining. The results show a statistical significant difference among PCIO indices for cutaneous genuine histiocytic lymphoma (CGHL), cutaneous germinal center cell-derived lymphomas (CGCCL), cutaneous peripheral T-cell lymphomas (CPTL), non-mycosis fungoides (MF) and Sezary's syndrome (SS), and MF when compared with those for CLI. There is a linear relationship between PCIO index and square root of PCIO density, both of which seem to have a parallel relationship to the severity of malignancy in CML. The nuclear volume of the positive tumor cell or lymphocyte with PCIO immunostaining may be also useful in differentiating CML from CLI.展开更多
Objective:Most patients with advanced lung cancer have a poor prognosis.Recent studies have identified TRIM59 as a novel molecule that serves as a prognostic factor for the progression of non-small cell lung cancer.In...Objective:Most patients with advanced lung cancer have a poor prognosis.Recent studies have identified TRIM59 as a novel molecule that serves as a prognostic factor for the progression of non-small cell lung cancer.In the present study,we investigated the role of TRIM59 in predicting the prognosis of lung adenocarcinoma(LUAD)as well as the correlation between TRIM59 expression and immune infiltrates.Methods:We analyzed TRIM59 expression in normal and tumor tissues based on RNA-sequencing datasets from The Cancer Genome Atlas and Genotype-Tissue Expression databases.Forty-seven cases of LUAD tissues and their matching adjacent tissues were collected,and TRIM59 expression in tissue samples was demonstrated by immunohistochemistry.All tissue specimens were obtained under the approval of the Medical Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine(approval No.IR2019001101;approved on April 3,2019).The immune cell scores were calculated using the CIBERSORT database.The Tumor Immune Estimation Resource database was used to analyze the correlation between TRIM59 and immune cell activities.Results:TRIM59 was up-regulated in most cancer types.High TRIM59 expression predicted a worse prognosis in patients with LUAD(overall survival,P=0.00096;disease-specific survival,P=0.00056;disease-free interval,P=0.0009;progression-free interval,P=0.0012).Moreover,TRIM59 was highly expressed in patients with LUAD who had a poorer prognosis.TRIM59 also showed a significant correlation with the ESTIMATE score(P=0.04)and stromal score(P=0.005)in patients with LUAD.Notably,a significant correlation between TRIM59 and the tumor mutation burden was found in LUAD but in no other cancer types(P<0.001).Further investigation showed that TRIM59 had a significant correlation with gene markers on neutrophils and dendritic cells.Conclusion:TRIM59 is a potential prognosticator in LUAD and may be correlated with immune cell identification,immune cell infiltration,and immunotherapy checkpoints in LUAD.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
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
基金National High Level Hospital Clinical Research Funding(Scientific Research Seed Fund of Peking University First Hospital).
文摘VEXAS(vacuoles,E1 enzyme,X-linked,autoinflammatory,somatic)syndrome is a severe and progressive disease,characterized by clinical features that bridge rheumatologic and hematologic conditions.[1]VEXAS syndrome is a rare condition that was not reported until 2020.[2]Since then,interest among dermatologists,hematologists,and rheumatologists with published works has increased,[3]but none of them reported in the emergency setting,nor have any cases arisen following COVID-19 infection.
文摘This work presents the results of investigations to develop and implement methods to effectively collect and purify infiltrates from heaps, situated in the region of Alwernia near Cracow, where more than 3 million tonnes of waste material resulting from the production of chromium compounds have been stored. It describes a system for the protection of groundwater from these infiltrates which contain 50-400 g m-3 Cr6+, as well as the effectiveness of cheap and simple chemical methods to purify these chromic wastewaters. The infiltrate collection system and the most effective method to decrease the concentration of Cr6+ to a level below 0.1 ppm, as required by Polish and European Union regulations, were implemented in the Alwernia Chemical Works S. A. in the years 1998-1999.
基金Supported by a grant from the Qingdao 2020 Medical Scientific Research Guidance Plan(No.2020-WJZD036).
文摘Enhancer of zeste homolog 2(EZH2)is the catalytic subunit of polycomb repressive complex 2(PRC2).Dysregulation of EZH2 causes alteration of gene expression and functions,thereby promoting cancer development.Recent studies suggest that EZH2 has a potential prognostic role in patients with nonsmall cell lung cancer(NSCLC).However,the prognostic value of EZH2 expression levels in NSCLC is controversial.In this study,we evaluated the prognostic value in lung cancer(LC-LUAD/LUSC)based on data from The Cancer Genome Atlas(TCGA)database.Kruskal-Wallis test,Wilcoxon signed-rank test,and logistic regression were used to evaluate the relationship between EZH2 expression and clinicopathological features.Cox regression and the Kaplan-Meier method were adopted to evaluate prognosis-related factors.Gene set enrichment analysis(GSEA)was performed to identify the key pathways related to EZH2.The correlations between EZH2 and cancer immune infiltrates were investigated by single-sample Gene Set Enrichment Analysis(ssGSEA).EZH2 was found to be up regulated with amplification in tumor tissues in multiple LC cohorts.High EZH2 expression was associated with poorer overall survival(OS).GSEA suggested that EZH2 regulates innate immune system,ECM affiliated,matrisome,surfactant metabolism.Notably,ssGSEA indicated that EZH2 expression was positively correlated with infiltrating levels of Th2 cells and significantly negatively correlated with mast cell infiltration level.These results suggest that EZH2 is associated with LC immune infiltration and significantly over-expressed in lung cancer,and its diagnostic value is better than prognosis,which lays a foundation for further study of the immunomodulatory role of EZH2 in LC.
基金funded by the Innovation Team Project of Hainan Natural Science Foundation(820CXTD446)the Technology Program of Qingyuan(No.2022KJJH027 to Linhai Li).
文摘Background: The protein encoded by ring finger protein 157 (RNF157) is known to function as an E3 ubiquitinligase. However, whether the level of RNF157 expression in breast cancer correlates with prognosis and immune cellinfiltration among breast cancer patients remains to be further explored. Methods: In this study, publicly availabledatasets were used for evaluating RNF157 expression in different tumors compared with normal samples. Severalindependent datasets were screened for investigating the relationship between RNF157 and breast cancer survival,different mutation profiles, and tumor immune cell infiltration. We conducted a pathway enrichment analysis toidentify signaling pathways associated with RNF157. Results: Analysis of public and online databases revealed thatRNF157 expression markedly decreased in breast cancer tissue samples compared to non-carcinoma counterparts.Consistently, immunohistochemistry assays also demonstrated this RNF157 down-regulation in breast cancer samples.RNF157 up-regulation could predict the improved survival of breast cancer cases. Further, different RNF157expression level groups exhibited different mutational profiles. Pathway enrichment profiling of RNF157-related genessuggested its possible involvement in regulating breast cancer via the mitogen-activated protein kinase (MAPK)pathway. RNA sequencing (RNA-seq) data and genomic enrichment analysis showed that RNF157 downregulatedseveral genes positively associated with the MAPK signaling pathway. We also explored RNF157 expression andimmune cell infiltration in breast cancer and found that RNF157 mRNA levels were negatively related to non-Timmune cell infiltration. Conclusion: According to our work, RNF157 may be a promising diagnostic biomarker andtherapeutic target for breast cancer.
基金Supported by grants from the National Natural Science Foundation of China(no.82001785)Chinese Society of Clinical Oncology(CSCO)-HengruiOncology Research Fund(No.Y-HR2020QN-0946).
文摘Background:Lung cancer,particularly lung adenocarcinoma(LUAD),is highly lethal.Understanding the critical interaction between epithelial-mesenchymal transition(EMT)and the immune status of patients is imperative for clinical assessment.Methods:We conducted bioinformatics analysis to identify potential immune-related EMT(iEMT)prognostic genes and explored the immune status in LUAD.Using data from The CancerGenome Atlas andGSE68465,differentially expressed genes,were identified,and a risk modelwas constructed.Cluster analysis was conducted using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways.Results:Our findings revealed 69 differentially expressed iEMT genes,with risk values demonstrating independent prognostic significance for both The Cancer Genome Atlas and GSE68465 samples.The risk value was positively correlated with tumor stage.Immune cell infiltration analysis showed a significant decrease in resting dendritic cells and an increase in CD4 memory T cells in high-risk groups with poor survival prognoses.The immunotherapy analysis revealed weak immunotherapeutic effects in the high-risk group.Conclusions:This study provides insights into potential aberrant differential iEMT genes and risk models and explores immune landscapes that inform personalized immunotherapy in patients with LUAD.
文摘Background:Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-related deaths globally.Splicing factor proline and glutamine-rich(SFPQ)is a multifunctional protein that controls various biological functions.As a potential therapeutic target and a promising prognostic indicator,the potential effects and processes of SFPQ in HCC require further investigation.Methods:The RNA sequencing data were obtained from the Gene Expression Omnibus,International Cancer Genome Consortium,and The Cancer Genome Atlas databases to analyze SFPQ expression and differentially expressed genes(DEGs).We utilized the LinkedOmics database to identify co-expressed genes.A Venn diagram was constructed to determine the overlapping genes between the DEGs and the co-expressed genes.Functional enrichment analysis was performed on the overlapping genes and DEGs.Furthermore,our study involved functional enrichment analysis,a protein-protein interaction network analysis,and an analysis of immune cell infiltration.The cBioPortal and Tumor Immune Single-cell Hub were utilized to investigate the genetic alterations of SFPQ and the single-cell transcriptome visualization of the tumor microenvironment.A ceRNA network was established with the assistance of the ENCORI website.Finally,we elucidated the clinical significance of SFPQ in HCC by employing Kaplan-Meier survival analysis,univariate and multivariate Cox regression,and prognostic nomogram models.Results:The expression of SFPQ in HCC tissues was significantly elevated compared to normal tissues.GSEA results indicated that increased expression of SFPQ was associated with pathways related to HCC.The ceRNA network,including SFPQ,hsa-miR-101-3p,AC023043.4,AC124798.1,AC145207.5,and GSEC,was constructed with the assistance of ENCORI.High SFPQ expression was related to a poor prognosis in HCC and its subtypes.Univariate and multivariate Cox regression analysis showed that elevated SFPQ expression is an independent predictive factor.Conclusions:The overexpression of SFPQ may serve as a potential prognostic biomarker,indicating a poor prognosis in HCC.
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This work was supported by a project funded by the National Natural Science Foundation of China (82260110,81870449,82170674,51933011)China Postdoctoral Science Foundation (2019M653904XB)Natural Science Foundation of Xinjiang Uyghur Autonomous Region (2020D01C006).
文摘Background:Hepatocellular carcinoma(HCC)is a leading cause of cancer-related death worldwide.The development of biomarkers for early detection and monitoring of HCC has not shown significant prog-ress.Meanwhile,the second adenomatous polyposis-related gene,MUTYH,which encodes a DNA gly-cosylase,has been observed in its contribution to oxidative DNA damage repair.Abnormal expression of MUTYH can reduce cell survival rate.Therefore,this study investigated the usefulness of MUTYH in diagnosing and prognosis HCC.Materials and methods:Using The Cancer Genome Atlas(TCGA)data,we analyzed the prognostic value of MUTYH in HCC.We used logistic regression,Wilcoxon signed-rank test,and KruskaleWallis test to examine MUTYH expression concerning clinical-pathologic characteristics.Univariate and multivariate Cox regression methods and Kaplan-Meier analysis were applied to determine the related prognostic factors of HCC.The enrichment analysis(GSEA)was used to determine the critical pathways associated with MUTYH.The single-sample gene set enrichment analysis(ssGSEA)was conducted to examine the correlation between MUTYH expression and cancer immune infiltration.Results:The higher expression of MUTYH in HCC patients was associated with a poorer overall survival rate and a shorter disease-specific survival rate.The Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis showed that all differentially expressed genes(DEGs)between the high and low expression levels of MUTYH significantly enriched in the trace ligand-receptor interaction,cell cycle,oocyte meiosis,gap junction,and DNA replication.Group analysis revealed the signals of their open access.The neuron system,M phase,DNA repair,Rho GTPase effector,and cell cycle checkpoints were significantly enriched.ssGSEA showed a positive correlation between MUTYH expression and the infiltration levels of Th2 cells,NK cells,and T helper cells.Moreover,a negative correlation was found between MUTYH expression and the infiltration levels of dendritic cells(DCs)and cytotoxic cells.Conclusions:MUTYH expression levels were positively correlated with immune checkpoint gene expression levels in HCC tissues.The expression level of MUTYH was related to the prognosis of HCC and the immune infiltration of HCC.
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the National natural science foundation of china
文摘Paraffin-embedded tissue of skin biopsy specimens taken retrospectively from 24 patients with cutaneous malignant lymphomas (CML) and 8 patients with cutaneous lymphoid infiltrates (CLI) and other dennatoses were studied retrospectively with PCIO immunostaining. The results show a statistical significant difference among PCIO indices for cutaneous genuine histiocytic lymphoma (CGHL), cutaneous germinal center cell-derived lymphomas (CGCCL), cutaneous peripheral T-cell lymphomas (CPTL), non-mycosis fungoides (MF) and Sezary's syndrome (SS), and MF when compared with those for CLI. There is a linear relationship between PCIO index and square root of PCIO density, both of which seem to have a parallel relationship to the severity of malignancy in CML. The nuclear volume of the positive tumor cell or lymphocyte with PCIO immunostaining may be also useful in differentiating CML from CLI.
基金This work is supported by the National Natural Science Foundation of China(No.81703072)The Natural Science Foundation of Zhejiang Province(No.LQ21H160027)。
文摘Objective:Most patients with advanced lung cancer have a poor prognosis.Recent studies have identified TRIM59 as a novel molecule that serves as a prognostic factor for the progression of non-small cell lung cancer.In the present study,we investigated the role of TRIM59 in predicting the prognosis of lung adenocarcinoma(LUAD)as well as the correlation between TRIM59 expression and immune infiltrates.Methods:We analyzed TRIM59 expression in normal and tumor tissues based on RNA-sequencing datasets from The Cancer Genome Atlas and Genotype-Tissue Expression databases.Forty-seven cases of LUAD tissues and their matching adjacent tissues were collected,and TRIM59 expression in tissue samples was demonstrated by immunohistochemistry.All tissue specimens were obtained under the approval of the Medical Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine(approval No.IR2019001101;approved on April 3,2019).The immune cell scores were calculated using the CIBERSORT database.The Tumor Immune Estimation Resource database was used to analyze the correlation between TRIM59 and immune cell activities.Results:TRIM59 was up-regulated in most cancer types.High TRIM59 expression predicted a worse prognosis in patients with LUAD(overall survival,P=0.00096;disease-specific survival,P=0.00056;disease-free interval,P=0.0009;progression-free interval,P=0.0012).Moreover,TRIM59 was highly expressed in patients with LUAD who had a poorer prognosis.TRIM59 also showed a significant correlation with the ESTIMATE score(P=0.04)and stromal score(P=0.005)in patients with LUAD.Notably,a significant correlation between TRIM59 and the tumor mutation burden was found in LUAD but in no other cancer types(P<0.001).Further investigation showed that TRIM59 had a significant correlation with gene markers on neutrophils and dendritic cells.Conclusion:TRIM59 is a potential prognosticator in LUAD and may be correlated with immune cell identification,immune cell infiltration,and immunotherapy checkpoints in LUAD.
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.
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.
