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
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
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
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
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
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:Cisplatin(DDP)has been used in the treatment of various human cancers.However,DDP alone lacks efficacy in treating triple-negative breast cancer(TNBC),and its clinical application is often hampered by side ...Background:Cisplatin(DDP)has been used in the treatment of various human cancers.However,DDP alone lacks efficacy in treating triple-negative breast cancer(TNBC),and its clinical application is often hampered by side effects.Astragalus polysaccharide(APS)is one of the active components extracted from Astragalus membranaceus and has gained attention for its various biological properties.This research is aimed to evaluate the effectiveness of a combination of APS and DDP on TNBC and explore the potential mechanisms.Methods:The efficacy and mechanisms of single or combined treatment were evaluated using Cell Counting Kit-8(CCK8)assay,Annexin V-fluorescein isothiocyanate(FITC)/propidium iodide(PI)staining,wound healing assay,trans-well invasion/migration assay,hematoxylin-eosin(HE)staining,immunohistochemical(IHC)staining,Western Blot(WB)analysis,and fluorescence-activated cell sorting(FACS).An orthotopic model of TNBC was used to assess the in vivo treatment efficacy of single or combination treatment.Results:APS significantly enhanced the anti-proliferative,anti-migratory,and anti-invasive effects of DDP on TNBC cells.The combination of APS and DDP downregulated anti-apoptotic genes(Bcl2 and Bcl-xL)while upregulating pro-apoptotic genes(Puma,Cle-Caspase3,Cle-PARP),leading to enhanced apoptosis.This combination treatment increased E-cadherin levels,decreased Vimentin,Snail,Slug,and Twist levels,and effectively suppressed epithelial-mesenchymal transition(EMT)-associated cell invasion.In the orthotopic model of TNBC,a synergistic reduction in tumor growth was observed in mice treated with APS and DDP.Additionally,the combination of APS and DDP induced the infiltration of CD8+T lymphocytes into the tumor immune microenvironment.Conclusion:The combination of APS and DDP exhibits more potent tumor inhibition and anti-tumor immunity than either agent alone,representing a novel approach to enhance therapeutic efficacy without increasing the side effects of DDP.展开更多
Based on the service characteristics of fuel elements for molten salt reactors,they need to have a high power density,resistance to coolant infiltration,and excellent thermodynamic properties.To solve the problem of t...Based on the service characteristics of fuel elements for molten salt reactors,they need to have a high power density,resistance to coolant infiltration,and excellent thermodynamic properties.To solve the problem of the graphite used in the fuel element for these reactors being susceptible to molten salt infiltration,carbon black(CB)was added to increase the density of the graphite,and a fuel element(TRISO(tri-structural isotropic)fuel particles were randomly distributed in the modified graphite matrix)was prepared by cold isostatic pressing process.An out-of-pile performance study shows that the densification and pore structure of the modified graphite matrix were improved,as was the resistance to molten salt infiltration.The median pore size of the modified graphite was reduced from 673 to 433 nm and the threshold pressure for molten salt(FLiBe,66%(molar fraction)LiF and 34%BeF_(2))infiltration was increased from 0.88 to 1.37 MPa.The isotropic CB made the graphite matrix less anisotropic,while its thermal conductivity and compressive strength were reduced due to the difficult graphitization of CB.Fuel elements containing 20%(volume fraction)TRISO particles were prepared.Numerical simulations show that the power and temperature distribution of the fuel were in line with the design requirements.The modified graphite matrix had a higher density,smaller pores,a lower anisotropy and a greater resistance to FLiBe infiltration.展开更多
Background:NDC80 is pivotal in cell division,particularly in regulating the G2/M transition and mitotic progression.Recent studies have demonstrated that NDC80 is significantly overexpressed in multiple solid tumors.F...Background:NDC80 is pivotal in cell division,particularly in regulating the G2/M transition and mitotic progression.Recent studies have demonstrated that NDC80 is significantly overexpressed in multiple solid tumors.Further analysis has suggested that its high expression is significantly associated with an elevated pathological grade,increased metastatic risk,and shortened overall survival in patients with cancer.However,its precise role in pan-cancer development,progression,and prognosis remains unclear.Methods:We conducted a multi-omics analysis of NDC80 using genomic,transcriptomic,and proteomic data from 33 cancer types in The Cancer Genome Atlas,Clinical Proteomic Tumor Analysis Consortium,Genotype-Tissue Expression,and Human Protein Atlas.Results:The results demonstrated frequent NDC80 mutations across multiple malignancies and significantly elevated expression in tumor tissues compared with that in their normal counterparts,correlating with worse overall and disease-free survival.Moreover,NDC80 expression was strongly associated with oncogenic pathways,key protein regulators,cellular components,myeloid-derived suppressor cell infiltration,ESTIMATE scores,and cancer-related signaling networks.Conclusions:These findings underscore the potential of NDC80 as a prognostic biomarker and therapeutic target for cancer treatment.展开更多
During the exploitation of sandstone gas reservoirs,natural fractures near the wellbore affect water infiltration and pore evolution;however,the impact mechanisms of these fractures remain unclear.This study utilized ...During the exploitation of sandstone gas reservoirs,natural fractures near the wellbore affect water infiltration and pore evolution;however,the impact mechanisms of these fractures remain unclear.This study utilized real-time nuclear magnetic resonance(RT-NMR)technology to investigate the influence of near-wellbore fracture angle(a)at 0°,15°,30°,and 45°on water infiltration,migration patterns,and pore evolution mechanisms during water injection.Throughout the experiments,T_(2)curves and magnetic resonance imaging(MRI)were monito red in real time during the water injection process.The pore evolution and water infiltration were translated by the evolution of T_(2)curves and MRI.The results show that increasing injection pressure(P_(inj))transforms adsorption pores into seepage pores,leading to enhanced pore damage.Pore damage predominantly occurs during the rapid pressurization stage and is concentrated around the near-wellbore fracture.The maximum infiltration area and rate were observed at α=0°,while the minimum values occurred at α=45°,which can be attributed to the significant influence of a on water infiltration and migration pathways.The increasing inclination of the infiltration front with a is attributed to the fact that the rate of water infiltration along the fracture wall is always higher than that at the fracture tip.In field fracturing,it is recommended to adjust the perforation direction to align with the natural fracture orientation and optimize pressurization strategies by reducing the slow pressurization duration while extending the rapid pressurization stage.These findings can provide important guidance for setting fracturing sections and optimizing injection parameters in sandstone gas reservoir exploitation.展开更多
To the Editor:Pancreatic cancer is a malignancy characterized by a poor prog-nosis,with a 5-year survival rate of<10%[1].Furthermore,only a minority of patients(<20%)qualify for curative-intent resec-tion,and ev...To the Editor:Pancreatic cancer is a malignancy characterized by a poor prog-nosis,with a 5-year survival rate of<10%[1].Furthermore,only a minority of patients(<20%)qualify for curative-intent resec-tion,and even among those who undergo this procedure,the risk of recurrence within three years remains alarmingly high,reach-ing up to 70%[2].Due to the lack of specific clinical manifes-tations of pancreatic cancer,most cases have metastasized or in-vaded the major vessels around the pancreas at the time of initial diagnosis,resulting in a low surgical resection rate.Even patients who undergo surgical resection often face a poor prognosis[3].In recent years,neoadjuvant chemotherapy using agents such as gemcitabine,5-fluorouracil,albumin-bound paclitaxel,modified fluorouracil/leucovorin plus irinotecan,and oxaliplatin(mFOLFIRI-NOX),targeted therapies addressing molecular subtypes of pan-creatic cancer,and immunotherapies targeting PD-1 and PD-L1 have shown efficacy in improving the overall prognosis of patients with pancreatic cancer,although the impact remains modest[4,5].Therefore,novel therapeutic strategies and prognostic evaluation systems are urgently needed to enhance the survival of patients with pancreatic cancer.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.
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 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.
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the Xuzhou Science and Technology Bureau,No.KC23186,Jiangsu Provincial Key Laboratory of New Drug Research and Clinical Pharmacy Project(No.XZSYSKF2023013)Key Medical Disciplines of Jiangsu Province’s 14th Five-Year Plan(ZDXK202237).
文摘Background:Cisplatin(DDP)has been used in the treatment of various human cancers.However,DDP alone lacks efficacy in treating triple-negative breast cancer(TNBC),and its clinical application is often hampered by side effects.Astragalus polysaccharide(APS)is one of the active components extracted from Astragalus membranaceus and has gained attention for its various biological properties.This research is aimed to evaluate the effectiveness of a combination of APS and DDP on TNBC and explore the potential mechanisms.Methods:The efficacy and mechanisms of single or combined treatment were evaluated using Cell Counting Kit-8(CCK8)assay,Annexin V-fluorescein isothiocyanate(FITC)/propidium iodide(PI)staining,wound healing assay,trans-well invasion/migration assay,hematoxylin-eosin(HE)staining,immunohistochemical(IHC)staining,Western Blot(WB)analysis,and fluorescence-activated cell sorting(FACS).An orthotopic model of TNBC was used to assess the in vivo treatment efficacy of single or combination treatment.Results:APS significantly enhanced the anti-proliferative,anti-migratory,and anti-invasive effects of DDP on TNBC cells.The combination of APS and DDP downregulated anti-apoptotic genes(Bcl2 and Bcl-xL)while upregulating pro-apoptotic genes(Puma,Cle-Caspase3,Cle-PARP),leading to enhanced apoptosis.This combination treatment increased E-cadherin levels,decreased Vimentin,Snail,Slug,and Twist levels,and effectively suppressed epithelial-mesenchymal transition(EMT)-associated cell invasion.In the orthotopic model of TNBC,a synergistic reduction in tumor growth was observed in mice treated with APS and DDP.Additionally,the combination of APS and DDP induced the infiltration of CD8+T lymphocytes into the tumor immune microenvironment.Conclusion:The combination of APS and DDP exhibits more potent tumor inhibition and anti-tumor immunity than either agent alone,representing a novel approach to enhance therapeutic efficacy without increasing the side effects of DDP.
文摘Based on the service characteristics of fuel elements for molten salt reactors,they need to have a high power density,resistance to coolant infiltration,and excellent thermodynamic properties.To solve the problem of the graphite used in the fuel element for these reactors being susceptible to molten salt infiltration,carbon black(CB)was added to increase the density of the graphite,and a fuel element(TRISO(tri-structural isotropic)fuel particles were randomly distributed in the modified graphite matrix)was prepared by cold isostatic pressing process.An out-of-pile performance study shows that the densification and pore structure of the modified graphite matrix were improved,as was the resistance to molten salt infiltration.The median pore size of the modified graphite was reduced from 673 to 433 nm and the threshold pressure for molten salt(FLiBe,66%(molar fraction)LiF and 34%BeF_(2))infiltration was increased from 0.88 to 1.37 MPa.The isotropic CB made the graphite matrix less anisotropic,while its thermal conductivity and compressive strength were reduced due to the difficult graphitization of CB.Fuel elements containing 20%(volume fraction)TRISO particles were prepared.Numerical simulations show that the power and temperature distribution of the fuel were in line with the design requirements.The modified graphite matrix had a higher density,smaller pores,a lower anisotropy and a greater resistance to FLiBe infiltration.
基金supported by grants from the Weifang Municipal Health Commission Research Programme Project(No.WFWSJK-2023-032)the Weifang Science and Technology Development Project(No.2023YX053)the Weifang Young Medical Talent Support Program Funding。
文摘Background:NDC80 is pivotal in cell division,particularly in regulating the G2/M transition and mitotic progression.Recent studies have demonstrated that NDC80 is significantly overexpressed in multiple solid tumors.Further analysis has suggested that its high expression is significantly associated with an elevated pathological grade,increased metastatic risk,and shortened overall survival in patients with cancer.However,its precise role in pan-cancer development,progression,and prognosis remains unclear.Methods:We conducted a multi-omics analysis of NDC80 using genomic,transcriptomic,and proteomic data from 33 cancer types in The Cancer Genome Atlas,Clinical Proteomic Tumor Analysis Consortium,Genotype-Tissue Expression,and Human Protein Atlas.Results:The results demonstrated frequent NDC80 mutations across multiple malignancies and significantly elevated expression in tumor tissues compared with that in their normal counterparts,correlating with worse overall and disease-free survival.Moreover,NDC80 expression was strongly associated with oncogenic pathways,key protein regulators,cellular components,myeloid-derived suppressor cell infiltration,ESTIMATE scores,and cancer-related signaling networks.Conclusions:These findings underscore the potential of NDC80 as a prognostic biomarker and therapeutic target for cancer treatment.
基金supported by National Natural Science Foundation of China(Nos.52364004,52464005)The Youth Talent Growth Project of Guizhou Provincial Department of Education(No.Qian Jiao Ji[2024]18)+3 种基金Postgraduate Research Fund of Guizhou Province in 2024(No.2024YJSKYJJ067)Basic Research Project of Guizhou University(No.[2023]40)Guizhou Provincial Basic Research Program(Natural Science)(No.Qian Ke He Ji Chu-ZK[2024]Yi Ban011)Research Fund for Talents of Guizhou University(No.Gui Da Ren Ji He Zi(2023)24)。
文摘During the exploitation of sandstone gas reservoirs,natural fractures near the wellbore affect water infiltration and pore evolution;however,the impact mechanisms of these fractures remain unclear.This study utilized real-time nuclear magnetic resonance(RT-NMR)technology to investigate the influence of near-wellbore fracture angle(a)at 0°,15°,30°,and 45°on water infiltration,migration patterns,and pore evolution mechanisms during water injection.Throughout the experiments,T_(2)curves and magnetic resonance imaging(MRI)were monito red in real time during the water injection process.The pore evolution and water infiltration were translated by the evolution of T_(2)curves and MRI.The results show that increasing injection pressure(P_(inj))transforms adsorption pores into seepage pores,leading to enhanced pore damage.Pore damage predominantly occurs during the rapid pressurization stage and is concentrated around the near-wellbore fracture.The maximum infiltration area and rate were observed at α=0°,while the minimum values occurred at α=45°,which can be attributed to the significant influence of a on water infiltration and migration pathways.The increasing inclination of the infiltration front with a is attributed to the fact that the rate of water infiltration along the fracture wall is always higher than that at the fracture tip.In field fracturing,it is recommended to adjust the perforation direction to align with the natural fracture orientation and optimize pressurization strategies by reducing the slow pressurization duration while extending the rapid pressurization stage.These findings can provide important guidance for setting fracturing sections and optimizing injection parameters in sandstone gas reservoir exploitation.
文摘To the Editor:Pancreatic cancer is a malignancy characterized by a poor prog-nosis,with a 5-year survival rate of<10%[1].Furthermore,only a minority of patients(<20%)qualify for curative-intent resec-tion,and even among those who undergo this procedure,the risk of recurrence within three years remains alarmingly high,reach-ing up to 70%[2].Due to the lack of specific clinical manifes-tations of pancreatic cancer,most cases have metastasized or in-vaded the major vessels around the pancreas at the time of initial diagnosis,resulting in a low surgical resection rate.Even patients who undergo surgical resection often face a poor prognosis[3].In recent years,neoadjuvant chemotherapy using agents such as gemcitabine,5-fluorouracil,albumin-bound paclitaxel,modified fluorouracil/leucovorin plus irinotecan,and oxaliplatin(mFOLFIRI-NOX),targeted therapies addressing molecular subtypes of pan-creatic cancer,and immunotherapies targeting PD-1 and PD-L1 have shown efficacy in improving the overall prognosis of patients with pancreatic cancer,although the impact remains modest[4,5].Therefore,novel therapeutic strategies and prognostic evaluation systems are urgently needed to enhance the survival of patients with pancreatic cancer.
