Machine learning(ML)provides a new surrogate method for investigating groundwater flow dynamics in unsaturated soils.Traditional pure data-driven methods(e.g.deep neural network,DNN)can provide rapid predictions,but t...Machine learning(ML)provides a new surrogate method for investigating groundwater flow dynamics in unsaturated soils.Traditional pure data-driven methods(e.g.deep neural network,DNN)can provide rapid predictions,but they do require sufficient on-site data for accurate training,and lack interpretability to the physical processes within the data.In this paper,we provide a physics and equalityconstrained artificial neural network(PECANN),to derive unsaturated infiltration solutions with a small amount of initial and boundary data.PECANN takes the physics-informed neural network(PINN)as a foundation,encodes the unsaturated infiltration physical laws(i.e.Richards equation,RE)into the loss function,and uses the augmented Lagrangian method to constrain the learning process of the solutions of RE by adding stronger penalty for the initial and boundary conditions.Four unsaturated infiltration cases are designed to test the training performance of PECANN,i.e.one-dimensional(1D)steady-state unsaturated infiltration,1D transient-state infiltration,two-dimensional(2D)transient-state infiltration,and 1D coupled unsaturated infiltration and deformation.The predicted results of PECANN are compared with the finite difference solutions or analytical solutions.The results indicate that PECANN can accurately capture the variations of pressure head during the unsaturated infiltration,and present higher precision and robustness than DNN and PINN.It is also revealed that PECANN can achieve the same accuracy as the finite difference method with fewer initial and boundary training data.Additionally,we investigate the effect of the hyperparameters of PECANN on solving RE problem.PECANN provides an effective tool for simulating unsaturated infiltration.展开更多
Infiltration–runoff–slope instability mechanism of macropore slope under heavy rainfall is unclear.This paper studied its instability mechanism with an improved Green–Ampt(GA)model considering the dual-porosity(i.e...Infiltration–runoff–slope instability mechanism of macropore slope under heavy rainfall is unclear.This paper studied its instability mechanism with an improved Green–Ampt(GA)model considering the dual-porosity(i.e.,matrix and macropore)and ponding condition,and proposed the infiltration equations,infiltration–runoff coupled model,and safety factor calculation method.Results show that the infiltration processes of macropore slope can be divided into three stages,and the proposed model is rational by a comparative analysis.The wetting front depth of the traditional unsaturated slope is 17.2%larger than that of the macropore slope in the early rainfall stage and 27%smaller than that of the macropore slope in the late rainfall stage.Then,macropores benefit the slope stability in the early rainfall but not in the latter.Macropore flow does not occur initially but becomes pronounced with increasing rainfall duration.The equal depth of the wetting front in the two domains is regarded as the onset criteria of macropore flow.Parameter analysis shows that macropore flow is delayed by increasing proportion of macropore domain(ω_(f)),whereas promoted by increasing ratio of saturated permeability coefficients between the two domains(μ).The increasing trend of ponding depth is sharp at first and then grows slowly.Finally,when rainfall duration is less than 3 h,ωf andμhave no significant effect on the safety factor,whereas it decreases with increasingωf and increases with increasingμunder longer duration(≥3 h).With the increase ofω_(f),the slope maximum instability time advances by 10.5 h,and with the increase ofμ,the slope maximum instability time delays by 3.1 h.展开更多
Diamond/aluminium composites have attracted attention in the field of thermal management of electronic packaging for their excellent properties.In order to solve the interfacial problem between diamond and aluminium,a...Diamond/aluminium composites have attracted attention in the field of thermal management of electronic packaging for their excellent properties.In order to solve the interfacial problem between diamond and aluminium,a novel process combining pressure infiltration with vacuum-assisted technology was proposed to prepare diamond/aluminum composites.The effect of diamond particle size on the microstructure and properties of the diamond/Al-12Si composites was investigated.The results show that the diamond/Al-12Si composites exhibit high relative density and a uniform microstructure.Both thermal conductivity and coefficient of thermal expansion increase with increasing particle size,while the bending strength exhibits the opposite trend.When the average diamond particle size increases from 45μm to 425μm,the thermal conductivity of the composites increases from 455 W·m^(-1)·K^(-1)to 713 W·m^(-1)·K^(-1)and the coefficient of thermal expansion increases from 4.97×10^(-6)K^(-1)to 6.72×10^(-6)K^(-1),while the bending strength decreases from 353 MPa to 246 MPa.This research demonstrates that high-quality composites can be prepared by the vacuum-assisted pressure infiltration process and the thermal conductivity of the composites can be effectively improved by increasing the diamond particle size.展开更多
Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is ...Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is limited research on the relationship between CRABP2 and immunotherapy response.This study found that negative correlations of CRABP2 and immune checkpoint markers(PD-1,PD-L1,and CTLA-4)were observed in breast invasive carcinoma(BRCA),skin cutaneous melanoma(SKCM),stomach adenocarcinoma(STAD)and testicular germ cell tumors(TGCT).In particular,in SKCM patients who were treated with PD-1 inhibitors,high levels of CRABP2 predicted poor prognosis.Additionally,CRABP2 expression was elevated in cancer-associated fibroblasts(CAFs)at the single-cell level.The expression of CRABP2 was positively correlated with markers of CAFs,such as MFAP5,PDPN,ITGA11,PDGFRα/βand THY1 in SKCM.To validate the tumor-promoting effect of CRABP2 in vivo,SKCM xenograft mice models with CRABP2 overexpression have been constructed.These models showed an increase in tumor weight and volume.Enrichment analysis indicated that CRABP2 may be involved in immunerelated pathways of SKCM,such as extracellular matrix(ECM)receptor interaction and epithelial-mesenchymal transition(EMT).The study suggests that CRABP2 may regulate immunotherapy in SKCM patients by influencing infiltration of CAFs.In conclusion,this study provides new insights into the role of CRABP2 in immunotherapy response.The findings suggest that CRABP2 may be a promising biomarker for PD-1 inhibitors in SKCM patients.Further research is needed to confirm these findings and to explore the clinical implications of CRABP2 in immunotherapy.展开更多
BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of ...BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of MTDH on stemness and immune infiltration in HCC.METHODS MTDH expression in HCC tissues was detected using TCGA and GEO databases.Immunohistochemistry was used to analyze the tissue samples.MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines.The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays.Next,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium.Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR.Flow cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like cells.The effects of MTDH inhibition on tumor growth were evaluated in vivo.The correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB databases.RESULTS HCC tissues expressed higher levels of MTDH than normal liver tissues.High MTDH expression was associated with a poor prognosis.HCC cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these effects.MTDH inhibition suppressed HCC progression and CD133 expression in vivo.MTDH was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T cells.MTDH was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression.CONCLUSION High levels of MTDH expression in patients with HCC are associated with poor prognosis,promoting tumor stemness,immune infiltration,and HCC progression.展开更多
BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the crit...BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the critical regulators and underlying molecular mechanisms remain largely unknown.AIM To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention.METHODS A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide(4NQO)to C57BL/6 mice.Moreover,we established a control group without 4NQO treatment of mice.Then,transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses,including low-grade IN(LGIN),high-grade IN(HGIN),and CA,and controlled normal tissue(NOR)samples.Differentially expressed genes(DEGs)were identified in the LGIN,HGIN,and CA groups,and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The CIBERSORT algorithm was used to detect the pattern of immune cell infilt-ration.Immunohistochemistry(IHC)was also conducted to validate our results.Finally,the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice.RESULTS Compared with those in the NOR group,a total of 681541,and 840 DEGs were obtained in the LGIN,HGIN,and CA groups,respectively.Using the intersection of the three sets of DEGs,we identified 86 genes as key genes involved in the development of ESCC.Enrichment analysis revealed that these genes were enriched mainly in the keratinization,epidermal cell differentiation,and interleukin(IL)-17 signaling pathways.CIBERSORT analysis revealed that,compared with those in the NOR group,M0 and M1 macrophages in the 4NQO group showed stronger infiltration,which was validated by IHC.Serum cytokine analysis revealed that,compared with those in the NOR group,IL-1βand IL-6 were upregulated,while IL-10 was downregulated in the LGIN,HGIN,and CA groups.Moreover,the expression of the representative key genes,such as S100a8 and Krt6b,was verified in external human samples,and the results of immunohistochemical staining were consistent with the findings in mice.CONCLUSION We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions.In addition,we found that macrophage infiltration and abnormal alterations in the levels of inflam-mation-associated cytokines,such as IL-1β,IL-6,and IL-10,in the peripheral blood may be closely associated with the development of ESCC.展开更多
Colorectal cancer(CRC)is a prevalent malignant tumor,with the global new cases reaching 1.9316 million and deaths reaching 935,200 in 2022.In China,therewere 555,500 new cases of CRC,with an age-standardized incidence...Colorectal cancer(CRC)is a prevalent malignant tumor,with the global new cases reaching 1.9316 million and deaths reaching 935,200 in 2022.In China,therewere 555,500 new cases of CRC,with an age-standardized incidence rate of 24.07 per 10million,and 286,200 deaths.China accounts for approximately 30%of new cases and deaths from CRC worldwide,with East Asia accounting for over 75%.Initially,CRC presents as local tumor growth,but it has the potential to spread to other body parts over time.Perineural infiltration(PNI)is a relatively less discussed route of diffusion,yet it plays a crucial role in the progression and prognosis of CRC.PNI often occurs alongside local lymph nodes and distant metastases,posing challenges for treatment and management.Clinical symptoms,radiographic findings,and histopathological examination can be used to diagnose PNI with skipmetastasis.Symptoms commonly include local pain,paresthesia,andmotor impairment.Imaging helps identify the mass’s location and relationship to nerves,whereas histopathological examination confirms the diagnosis.Treatment of PNI skipmetastases is similar to other CRC metastases,including surgical resection,chemotherapy,radiotherapy,and targeted therapy.Surgical resection is the primary therapeutic approach,but the wider range of metastasis in PNI skip transfer may limit its feasibility.In cases where surgical resection is not possible,chemotherapy,radiotherapy,and targeted therapy are used to control tumor metastasis.In conclusion,PNI skip metastases increase the risk of poor prognosis for CRC,requiring a comprehensive approach with multiple treatments to prevent disease progression.Early detection and treatment are vital to improving prognosis.展开更多
Background: A major cause of cancer death worldwide is bladder cancer, which is the most common malignant tumor of the urinary tract. PAEP is a member of the kernel lipocalin superfamily whose members share relatively...Background: A major cause of cancer death worldwide is bladder cancer, which is the most common malignant tumor of the urinary tract. PAEP is a member of the kernel lipocalin superfamily whose members share relatively low sequence similarity but have highly conserved exon/intron structure and three-dimensional protein folding. Most lipocalins are clustered on the long arm of chromosome 9. The purpose of this study was to clarify the correlation between PAEP expression level and bladder cancer. Methods: In the TCGA database, we obtained clinical and RNA sequencing data of 431 BLCA patients, including 412 BLCA tissues and 19 normal bladder tissues in the study. Analyses of bioinformatics were conducted in this study to determine the role of PAEP in bladder cancer. A quantitative real-time PCR method was used to quantitate the gene expression profile. Additionally, the effect of PAEP on tumor immune infiltration and prognosis was analyzed. Results: PAEP was a poor prognostic biomarker of bladder cancer because it was significantly upregulated. bladder cancer patients with higher PAEP expression had poor outcomes. An AUC of 0.780 was calculated from the area under the ROC curve. PAEP was associated with T stage, pathologic stage, Histologic grade and Subtype of bladder cancer patients, and served as an independent predictor of overall survival in bladder cancer patients. Functional enrichment analysis revealed PAEP was obviously enriched in pathways connected with carcinogenesis and immunosuppression. The expression of PAEP was significantly associated with tumor immune cells and immune checkpoints according to ssGSEA and Spearman correlation analysis. Conclusions: In this study, we screened and detected a mRNA, PAEP is a prognostic and immune-related biomarker in BLCA, which may contribute to the early diagnosis and treatment of BLCA.展开更多
Background:The molecular mechanism underlying the involvement of the Transferrin receptor(TFRC)in cervical cancer remains poorly understood.This study aims to elucidate the role of TFRC in cervical cancer by analyzing...Background:The molecular mechanism underlying the involvement of the Transferrin receptor(TFRC)in cervical cancer remains poorly understood.This study aims to elucidate the role of TFRC in cervical cancer by analyzing data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.Methods:TFRC protein expression was obtained from Human Protein Altas(HPA).All datas were collected from TCGA and GTEx.In this study,we analyzed the expression of TFRC in cervical cancer and its clinical significance.Through Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene set enrichment analyses(GSEA),investigated the related molecular pathways of TFRC.The relationship between TFRC and immune infiltration was then examined.The prognosis of different immune cell subsets was then analyzed after dividing cervical cancer patients into high and low expression of TFRC groups.Results:TFRC is highly expressed in various tumor tissues compared to control normal tissues,including cervical cancer.An increased expression of TFRC was associated with higher Tumor(T)and Node(N)stage,as well as a higher clinical stage.Kaplan–Meier(KM)survival analysis investigated that higher TFRC expression patients have a poor overall survival(OS),disease specific survival(DSS)and progress free interval(PFI).Both KEGG and GSEA enriched signaling pathway by high TFRC and low TFRC groups.There was a significant negative linear correlation between TFRC expression and immune infiltration.TFRC affects the prognosis of cervical cancer patients through immune pathway.Conclusions:Cervical cancer patients with TFRC expression may have a worse prognosis.展开更多
Background:Owing to the occurrence of primary or secondary tolerance,the efficacy of immunotherapy for hepatocellular carcinoma(HCC)patients is limited.Therefore,the mechanism underlying this tolerance needs to be fur...Background:Owing to the occurrence of primary or secondary tolerance,the efficacy of immunotherapy for hepatocellular carcinoma(HCC)patients is limited.Therefore,the mechanism underlying this tolerance needs to be further investigated.B cell–specific Moloney murine leukemia virus integration site 1(BMI1)is associated with cancer stem cell tumorigenesis,progression,and the maintenance of the self-renewal.However,the effect of BMI1 expression on immune infiltration and prognosis in HCC is still unclear.Methods:To assess the relationship between BMI1 expression and HCC prognosis and immune infiltration,the GEPIA database,TIMER database,and K-M plotter were used.TIMER database was used to determine the levels ofBMI1 in various tumor tissues and corresponding normal tissues,and examine the association between BMI1 expression and tumor-infiltrating immune cells.GEPIA database was applied to determine BMI1 expression in various tumor tissues and corresponding normal tissues.K-M Plotter was used to study the relationships among BMI1 expression,clinicopathological features,and survival rates.Results:BMI1 expression was markedly higher in various solid tumors compared with that in the respective normal tissues,including HCC,and high expression led to poor relapse-free survival and overall survival in HCC patients.BMI1 overexpression was also correlated with the infiltration of immune cells(eg,B cells,CD8+T cells,CD4+T cells,dendritic cells,neutrophils,and macrophages)and positively associated with different subsets of T cells,monocytes,and M1 macrophages,among others.Conclusions:This study demonstrates that high BMI1 expression is strongly correlated with immune infiltration and poor prognosis in HCC.Increased expression of BMI1 might thus be a potential mechanism of immune tolerance in this disease.展开更多
Infiltration is an important part of the hydrological cycle, and it is one of the main abstractions accounted for in the rainfall-runoff modeling. The main purpose of this study is to compare the infiltration models t...Infiltration is an important part of the hydrological cycle, and it is one of the main abstractions accounted for in the rainfall-runoff modeling. The main purpose of this study is to compare the infiltration models that were used to assess the infiltration rate of the Mitidja Plain in Algeria. Field infiltration tests were conducted at 40 different sites using a double ring infiltrometer. Five statistical comparison criteria including root mean squared error(RMSE), normalized root mean squared error(NRMSE), coefficient of correlation(CC), Nash-Sutcliffe efficiency(NSE), and Kling-Gupta efficiency(KGE) were used to determine the best performing infiltration model and to confirm anomalies between predicted and observed values. Then we evaluated performance of five models(i.e., the Philip model, Kostiakov model, Modified Kostiakov model, Novel model, and Horton model) in simulating the infiltration process based on the adjusted performance parameters cited above. Results indicated that the Novel model had the best simulated water infiltration process in the Mitidja Plain in Algeria. However, the Philip model was the weakest to simulate the infiltration process. The conclusion of this study can be useful for estimating infiltration rate at various sites using a Novel model when measured infiltration data are not available and are useful for planning and managing water resources in the study area.展开更多
Background:Cytochrome b561(CYB561)plays a critical role in neuroendocrine function,cardiovascular regulation,and tumor growth;however,the prognostic value of CYB561 in patients with breast cancer and the relationship ...Background:Cytochrome b561(CYB561)plays a critical role in neuroendocrine function,cardiovascular regulation,and tumor growth;however,the prognostic value of CYB561 in patients with breast cancer and the relationship between CYB561 expression and immune infiltration in breast cancer remain unclear.Methods:The mRNA expression and clinical data of patients with breast cancer were obtained from The Cancer Genome Atlas database.Functional enrichment analysis was used to explore underlying biological functions associated with CYB561.The methylation status of CYB561 was analyzed using the MethSurv database.The enrichment score of immune cell infiltration for CYB561 in breast cancer was calculated using single-sample gene set enrichment analysis.The prognostic value of CYB561 was evaluated using Kaplan-Meier method and Cox regression analysis.Based on the results of the multivariate Cox analysis,a nomogram was constructed to predict the effect of CYB561 expression on overall survival(OS).Results:The results showed that CYB561 was highly expressed in breast cancer tissues.Hypomethylation of CYB561 is associated with an unfavorable prognosis.In multivariate Cox regression analysis,CYB561 was an independent prognostic factor for OS.Functional enrichment analysis indicated that estrogen signaling pathway,inflammatory response,KRAS signaling pathway,epithelial-mesenchymal transition,leukocyte migration,and regulation of lymphocyte activation were strongly enriched in the low CYB561 expression group.Additionally,CYB561 expression was negatively correlated with immune infiltration of B cells,plasmacytoid dendritic cells,dendritic cells,and neutrophils.Conclusion:CYB561 may serve as a potential biomarker for breast cancer diagnosis and prognosis.展开更多
The flexible pressure sensor has been credited for leading performance including higher sensitivity,faster response/recovery,wider detection range and higher mechanical durability,thus driving the development of novel...The flexible pressure sensor has been credited for leading performance including higher sensitivity,faster response/recovery,wider detection range and higher mechanical durability,thus driving the development of novel sensing materials enabled by new processing technologies.Using atomic layer infiltration,Pt nanocrystals with dimensions on the order of a few nanometers can be infiltrated into the compressible lamellar structure of Ti3C2Tx MXene,allowing a modulation of its interlayer spacing,electrical conductivity and piezoresistive property.The flexible piezoresistive sensor is further developed from the Pt-infiltrated MXene on a paper substrate.It is demonstrated that Pt infiltration leads to a significant enhancement of the pressure-sensing performance of the sensor,including increase of sensitivity from 0.08 kPa^(-1)to 0.5 kPa^(-1),extension of detection limit from 5 kPa to 9 kPa,decrease of response time from 200 ms to 20 ms,and reduction of recovery time from 230 ms to 50 ms.The mechanical durability of the flexible sensor is also improved,with the piezoresistive performance stable over 1000 cycles of flexure fatigue.The atomic layer infiltration process offers new possibilities for the structure modification of MXene for advanced sensor applications.展开更多
BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is a malignant tumor of the hepatobiliary system with concealed onset,strong invasiveness and poor prognosis.AIM To explore the disease characteristic genes that may be h...BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is a malignant tumor of the hepatobiliary system with concealed onset,strong invasiveness and poor prognosis.AIM To explore the disease characteristic genes that may be helpful in the diagnosis of ICC and affect immune cell infiltration.METHODS We downloaded two ICC-related human gene expression profiles from GEO database as the training group(GSE26566 and GSE32958 datasets)for difference analysis,and performed enrichment analysis on differential genes.The least absolute shrinkage and selection operator(LASSO),support vector machinerecursive feature elimination(SVM-RFE)and random forest(RF),three machine learning algorithms,were used to screen the characteristic genes.Double verification was carried out on GSE107943 and The Cancer Genome Atlas,two verification groups.Receiver operating characteristic curve and area under the curve(AUC)were used to evaluate the diagnostic efficacy of genes for ICC.CIBERSORT and ssGSEA algorithms were used to evaluate the effect of characteristic genes on immune infiltration pattern.Human Protein Atlas(HPA)was used to analyze the protein expression level of the target gene.RESULTS A total of 1091 differential genes were obtained in the training group.Enrichment analysis showed that the above genes were mainly enriched in small molecular catabolism,complement and coagulation cascade,bile secretion and other functions and pathways.Twentyfive characteristic genes were screened by LASSO regression,19 by SVM-RFE algorithm,and 30 by RF algorithm.Three algorithms were used in combination to determine the characteristic gene of ICC:MMP14.The verification group confirmed that the genes had a high diagnostic accuracy(AUC values of the training group and the verification group were 0.960,0.999,and 0.977,respectively).Comprehensive analysis of immune infiltration showed that MMP14 could affect the infiltration of monocytes,activated memory CD4 T cells,resting memory CD4 T cells,and other immune cells,and was closely related to the expression of CD200,cytotoxic T-lymphocyteassociated antigen 4,CD14,CD44,and other immune checkpoints.The results of immunohistochemistry in HPA database showed was indeed overexpressed in ICC.CONCLUSION MMP14 can be used as a disease characteristic gene of ICC,and may regulate the distribution of immune-infiltrating cells in the ICC tumor microenvironment,which provides a new method for the determination of ICC diagnostic markers and screening of therapeutic targets.展开更多
Hepatocellular carcinoma(HCC)is the most common fatal cancer worldwide,patients with HCC have a high mortality rate and poor prognosis.PANoptosis is a novel discovery of programmed cell death associated with cancer de...Hepatocellular carcinoma(HCC)is the most common fatal cancer worldwide,patients with HCC have a high mortality rate and poor prognosis.PANoptosis is a novel discovery of programmed cell death associated with cancer development.However,the role of PANoptosis in HCC remains obscure.In this study,we enrolled 274 PANoptosisrelated genes(PANRGs)and screened 8 genes to set up a prognostic model.A previous scoring system calculated PANscore was utilized to quantify the individual risk level of each HCC patient,and the reliability of the prognostic model has been validated in an external cohort.Nomogram constructed with PANscore and clinical characteristics were used to optimize individualized treatment for each patient.Single-cell analysis revealed a PANoptosis model associated with tumor immune cell infiltration,particularly natural killer(NK)cells.Further exploration of hub genes and assessment of the prognostic role of these 4 hub genes in HCC by quantitative real-time PCR(qRT-PCR)and immunohistochemistry(IHC).In conclusion,we evaluated a PANoptosis-based prognostic model as a potential prognostic biomarker for HCC patients.展开更多
ZrC_(x)-NbC_(y)-Cu composites were fabricated by pressure-less reactive infiltration of Zr-Cu binary melts into porous NbC preforms at 1300℃.The effect of Zr content in the infiltrator on microstructure of the as-syn...ZrC_(x)-NbC_(y)-Cu composites were fabricated by pressure-less reactive infiltration of Zr-Cu binary melts into porous NbC preforms at 1300℃.The effect of Zr content in the infiltrator on microstructure of the as-synthesized composites was studied.Mechanical properties of the composites were reported.A partial displacement of Nb atoms in NbC by Zr atoms from Zr-Cu melt occurs during the reaction between Zr-Cu melt and porous NbC preform.The formation of a core-shell structure suggests the reaction is mainly a dissolutionprecipitation type.NbC dissolves into Zr-Cu melt,from which the(Nb,Zr)C_(z)phase precipitates and grows.With increasing Zr content in the Zr-Cu infiltrator,the reaction is enhanced and the infiltration is easily chocked.ZrC_(x)-NbC_(y)-Cu composite is synthesized using Zr_(14)Cu_(51)infiltrator.The flexural strength and fracture toughness of ZrC_(x)-NbC_(y)-Cu composite reach 637 MPa and 12.7 MPa·m^(1/2),respectively.And the improved toughness is probably attributed to residual Cu phase and plate-like Nb_(x)C_(y)phases.展开更多
Objective Diffuse large B-cell lymphoma(DLBCL)is often associated with bone marrow infiltration,and 2-deoxy-2-(18F)fluorodeoxyglucose positron emission tomography/computed tomography(^(18)F-FDG PET/CT)has potential di...Objective Diffuse large B-cell lymphoma(DLBCL)is often associated with bone marrow infiltration,and 2-deoxy-2-(18F)fluorodeoxyglucose positron emission tomography/computed tomography(^(18)F-FDG PET/CT)has potential diagnostic significance for bone marrow infiltration in DLBCL.Methods A total of 102 patients diagnosed with DLBCL between September 2019 and August 2022 were included.Bone marrow biopsy and^(18)F-FDG PET/CT examinations were performed at the time of initial diagnosis.Kappa tests were used to evaluate the agreement of^(18)F-FDG PET/CT with the gold standard,and the imaging features of DLBCL bone marrow infiltration on PET/CT were described.Results The total detection rate of bone marrow infiltration was not significantly different between PET/CT and primary bone marrow biopsy(P=0.302)or between the two bone marrow biopsies(P=0.826).The sensitivity,specificity,and Youden index of PET/CT for the diagnosis of DLBCL bone marrow infiltration were 0.923(95%CI,0.759-0.979),0.934(95%CI,0.855-0.972),and 0.857,respectively.Conclusion^(18)F-FDG PET/CT has a comparable efficiency in the diagnosis of DLBCL bone marrow infiltration.PET/CT-guided bone marrow biopsy can reduce the misdiagnosis of DLBCL bone marrow infiltration.展开更多
Glutamine metabolism(GM)plays an important role in tumor growth and proliferation.Skin cutaneous melanoma(SKCM)is a glutamine-dependent cancer.However,the molecular characteristics and action mechanism of GM on SKCM r...Glutamine metabolism(GM)plays an important role in tumor growth and proliferation.Skin cutaneous melanoma(SKCM)is a glutamine-dependent cancer.However,the molecular characteristics and action mechanism of GM on SKCM remain unclear.Therefore,we aimed to explore the effects of GM-related genes on survival,clinicopathological characteristics,and the tumor microenvironment in SKCM.In this study,682 SKCM samples were obtained from the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.Consensus clustering was used to classify SKCM samples into distinct subtypes based on 41 GM-related genes.Differences in survival,immune infiltration,clinical characteristics,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways as well as differentially expressed genes(DEGs)between subgroups were evaluated.A prognostic model was constructed according to prognostic DEGs.Differential analyses in survival,immune infiltration,tumor microenvironment(TME),tumor mutation burden(TMB),stemness,and drug sensitivity between risk groups were conducted.We identified two distinct GM-related subtypes on SKCM and found that GM-related gene alterations were associated with survival probability,clinical features,biological function,and immune infiltration.Then a risk model based on six DEGs(IL18,SEMA6A,PAEP,TNFRSF17,AIM2,and CXCL10)was constructed and validated for predicting overall survival in SKCM patients.The results showed that the risk score was negatively correlated with CD8+T cells,activated CD4+memory T cells,M1 macrophages,andγδT cells.The group with a low-risk score was accompanied by a better survival rate with higher TME scores and lower stemness index.Moreover,the group with high-and low-risk score had a significant difference with the sensitivity of 75 drugs(p<0.001).Overall,distinct subtypes in SKCM patients based on GM-related genes were identified and the risk model was constructed,which might contribute to prognosis prediction,guide clinical therapy,and develop novel therapeutic strategies.展开更多
BACKGROUND Gastric cancer(GC)is a malignant tumor with high morbidity and mortality.Expression of COL5A2 is significantly elevated in GC.Abnormal expression of noncoding RNAs(ncRNAs)have been found in GC,including mic...BACKGROUND Gastric cancer(GC)is a malignant tumor with high morbidity and mortality.Expression of COL5A2 is significantly elevated in GC.Abnormal expression of noncoding RNAs(ncRNAs)have been found in GC,including microRNA(miRNA)and long noncoding RNA(lncRNA).Competing endogenous RNA network plays an important regulatory role in GC.However,its specific regulatory mechanism has not been elucidated.AIM To gain insight into the ncRNA regulatory mechanism and immune microenvironment related to COL5A2 in GC.METHODS RNA sequencing data and clinical information from The Cancer Genome Atlas data portal were used to analyze the expressions of COL5A2,miRNA and lncRNA related to the prognosis of GC.Cox regression analysis and Kyoto Encyclopedia of Genes and Genomes analysis were performed to assess the risk factors and relevant function of COL5A2.StarBase was used to predict the interaction of miRNA–lncRNA or miRNA–mRNA in GC.The relationship between COL5A2,miR-144-3p and ENTPD1-AS1 were verified by dual luciferase reporter assay.The association of COL5A2 with immune cell infiltration were analyzed using the Tumor Immune Estimation Resource database and single sample gene set enrichment analysis.The expression of COL5A2 and macrophages in paired GC tissues were detected by immunohistochemical staining.RESULTS We verified that the upregulation of COL5A2 expression was associated with the prognosis of GC and was an independent risk factor for GC.miR-144-3p was downregulated and correlated with the prognosis of GC.miR-144-3p regulated the expression of COL5A2 through direct interaction with COL5A2.ENTPD1-AS1 was elevated in GC and competitively bound to miR-144-3p,thus inhibiting the expression of miR-144-3p.ENTPD1-AS1 enhanced the expression of COL5A2 through sponging miR-144-3p.Compared to paired normal tissue,COL5A2 expression was upregulated at the protein level,especially in the middle and late stages of GC.The high expression of COL5A2 was positively linked to macrophage infiltration in GC.CONCLUSION COL5A2 regulated by ENTPD1-AS1–miR-144-3p was associated with poor prognosis and macrophage infiltration in GC.This could be a new biomarker and therapeutic target in GC.展开更多
Objective:Constructing a prognostic model for gastric cancer(GC)based on cuproptosisrelated LncRNAs(CRLs)and predict the traditional Chinese medicine that regulate cuproptosis-related genes(CRGs).Methods:Clinical data...Objective:Constructing a prognostic model for gastric cancer(GC)based on cuproptosisrelated LncRNAs(CRLs)and predict the traditional Chinese medicine that regulate cuproptosis-related genes(CRGs).Methods:Clinical data and RNA-seq of 443 GC cases were obtained from The Cancer Genome Atlas(TCGA)database,and CRLs were screened by Pearson analysis,Cox regression,and least absolute shrinkage and selection operator(LASSO)regression to construct a risk model to predict GC prognosis,and the nomogram was constructed by combining risk scores and clinical characteristics.The accuracy of the model was validated by the receiver operating characteristic curve,Kaplan-Meier curves and C-index.To assess the correlation of risk scores with immune infiltration,immune checkpoint gene expression and chemotherapy/targeted agents.The Coremine Medical database was applied to predict potential traditional Chinese medicine that regulate CRGs.Results:Risk models for GC were constructed based on the risk scores of seven CRLs(AP001107.9,VCAN-AS1,AC016394.2,LINC02675,AC100814.1,HAGLR,and LINC01094).The AUC of the risk model predicting 1-,3-,and 5-year survival in GC patients was 0.720,0.682,and 0.711,and its prognostic value was better than age,Grade classification,and TNM stage.The AUC of the risk model combining age and TNM stage to predict 1-year survival in GC patients was 0.793.The risk score correlated with the degree of enrichment of immune cells such as tumorinfiltrating lymphocytes and regulatory T cells and the expression of 22 immune checkpoint genes such as LAG3,ICOS,CD28,NRP1 and the sensitivity of 13 chemotherapeutic/targeted agents.There are 58 traditional Chinese medicine with potential regulatory effects on CRGs,mainly for clearing heat and detoxing,promoting blood circulation and relieving pain,which are mainly attributed to the liver,spleen and lung meridians.Spirulina and osthole have potential regulatory effects on FDX1,a key gene in the death mechanism of cuproptosis.Conclusions:A risk signature constructed based on seven CRLs could assess the prognosis and immunity of GC,and Spirulina and Serpentine may have important regulatory efficacy on the mechanism of copper cuproptosis.展开更多
基金funding support from the science and technology innovation Program of Hunan Province(Grant No.2023RC1017)Hunan Provincial Postgraduate Research and Innovation Project(Grant No.CX20220109)National Natural Science Foundation of China Youth Fund(Grant No.52208378).
文摘Machine learning(ML)provides a new surrogate method for investigating groundwater flow dynamics in unsaturated soils.Traditional pure data-driven methods(e.g.deep neural network,DNN)can provide rapid predictions,but they do require sufficient on-site data for accurate training,and lack interpretability to the physical processes within the data.In this paper,we provide a physics and equalityconstrained artificial neural network(PECANN),to derive unsaturated infiltration solutions with a small amount of initial and boundary data.PECANN takes the physics-informed neural network(PINN)as a foundation,encodes the unsaturated infiltration physical laws(i.e.Richards equation,RE)into the loss function,and uses the augmented Lagrangian method to constrain the learning process of the solutions of RE by adding stronger penalty for the initial and boundary conditions.Four unsaturated infiltration cases are designed to test the training performance of PECANN,i.e.one-dimensional(1D)steady-state unsaturated infiltration,1D transient-state infiltration,two-dimensional(2D)transient-state infiltration,and 1D coupled unsaturated infiltration and deformation.The predicted results of PECANN are compared with the finite difference solutions or analytical solutions.The results indicate that PECANN can accurately capture the variations of pressure head during the unsaturated infiltration,and present higher precision and robustness than DNN and PINN.It is also revealed that PECANN can achieve the same accuracy as the finite difference method with fewer initial and boundary training data.Additionally,we investigate the effect of the hyperparameters of PECANN on solving RE problem.PECANN provides an effective tool for simulating unsaturated infiltration.
基金funded by the Natural Science Foundation of Fujian Province(Grant No.2023J011133)。
文摘Infiltration–runoff–slope instability mechanism of macropore slope under heavy rainfall is unclear.This paper studied its instability mechanism with an improved Green–Ampt(GA)model considering the dual-porosity(i.e.,matrix and macropore)and ponding condition,and proposed the infiltration equations,infiltration–runoff coupled model,and safety factor calculation method.Results show that the infiltration processes of macropore slope can be divided into three stages,and the proposed model is rational by a comparative analysis.The wetting front depth of the traditional unsaturated slope is 17.2%larger than that of the macropore slope in the early rainfall stage and 27%smaller than that of the macropore slope in the late rainfall stage.Then,macropores benefit the slope stability in the early rainfall but not in the latter.Macropore flow does not occur initially but becomes pronounced with increasing rainfall duration.The equal depth of the wetting front in the two domains is regarded as the onset criteria of macropore flow.Parameter analysis shows that macropore flow is delayed by increasing proportion of macropore domain(ω_(f)),whereas promoted by increasing ratio of saturated permeability coefficients between the two domains(μ).The increasing trend of ponding depth is sharp at first and then grows slowly.Finally,when rainfall duration is less than 3 h,ωf andμhave no significant effect on the safety factor,whereas it decreases with increasingωf and increases with increasingμunder longer duration(≥3 h).With the increase ofω_(f),the slope maximum instability time advances by 10.5 h,and with the increase ofμ,the slope maximum instability time delays by 3.1 h.
文摘Diamond/aluminium composites have attracted attention in the field of thermal management of electronic packaging for their excellent properties.In order to solve the interfacial problem between diamond and aluminium,a novel process combining pressure infiltration with vacuum-assisted technology was proposed to prepare diamond/aluminum composites.The effect of diamond particle size on the microstructure and properties of the diamond/Al-12Si composites was investigated.The results show that the diamond/Al-12Si composites exhibit high relative density and a uniform microstructure.Both thermal conductivity and coefficient of thermal expansion increase with increasing particle size,while the bending strength exhibits the opposite trend.When the average diamond particle size increases from 45μm to 425μm,the thermal conductivity of the composites increases from 455 W·m^(-1)·K^(-1)to 713 W·m^(-1)·K^(-1)and the coefficient of thermal expansion increases from 4.97×10^(-6)K^(-1)to 6.72×10^(-6)K^(-1),while the bending strength decreases from 353 MPa to 246 MPa.This research demonstrates that high-quality composites can be prepared by the vacuum-assisted pressure infiltration process and the thermal conductivity of the composites can be effectively improved by increasing the diamond particle size.
基金supported by grants from the Natural Science Foundation of Hunan Province(2022JJ80044)the Youth Science Foundation of Xiangya Hospital(2019Q13).
文摘Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is limited research on the relationship between CRABP2 and immunotherapy response.This study found that negative correlations of CRABP2 and immune checkpoint markers(PD-1,PD-L1,and CTLA-4)were observed in breast invasive carcinoma(BRCA),skin cutaneous melanoma(SKCM),stomach adenocarcinoma(STAD)and testicular germ cell tumors(TGCT).In particular,in SKCM patients who were treated with PD-1 inhibitors,high levels of CRABP2 predicted poor prognosis.Additionally,CRABP2 expression was elevated in cancer-associated fibroblasts(CAFs)at the single-cell level.The expression of CRABP2 was positively correlated with markers of CAFs,such as MFAP5,PDPN,ITGA11,PDGFRα/βand THY1 in SKCM.To validate the tumor-promoting effect of CRABP2 in vivo,SKCM xenograft mice models with CRABP2 overexpression have been constructed.These models showed an increase in tumor weight and volume.Enrichment analysis indicated that CRABP2 may be involved in immunerelated pathways of SKCM,such as extracellular matrix(ECM)receptor interaction and epithelial-mesenchymal transition(EMT).The study suggests that CRABP2 may regulate immunotherapy in SKCM patients by influencing infiltration of CAFs.In conclusion,this study provides new insights into the role of CRABP2 in immunotherapy response.The findings suggest that CRABP2 may be a promising biomarker for PD-1 inhibitors in SKCM patients.Further research is needed to confirm these findings and to explore the clinical implications of CRABP2 in immunotherapy.
基金National Natural Science Foundation of China,No.82173359Basic Research and Frontier Exploration Project of Chongqing and Technology Commission,No.cstc2018jcyjAX0181Kuanren Talents Program of The Second Affiliated Hospital of Chongqing Medical University.
文摘BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of MTDH on stemness and immune infiltration in HCC.METHODS MTDH expression in HCC tissues was detected using TCGA and GEO databases.Immunohistochemistry was used to analyze the tissue samples.MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines.The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays.Next,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium.Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR.Flow cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like cells.The effects of MTDH inhibition on tumor growth were evaluated in vivo.The correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB databases.RESULTS HCC tissues expressed higher levels of MTDH than normal liver tissues.High MTDH expression was associated with a poor prognosis.HCC cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these effects.MTDH inhibition suppressed HCC progression and CD133 expression in vivo.MTDH was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T cells.MTDH was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression.CONCLUSION High levels of MTDH expression in patients with HCC are associated with poor prognosis,promoting tumor stemness,immune infiltration,and HCC progression.
基金Supported by National Natural Foundation of China,No.821742232019 Chinese and Western Medicine Clinical Collaborative Capacity Building Project for Major Difficult Diseases,No.2019-ZX-005。
文摘BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the critical regulators and underlying molecular mechanisms remain largely unknown.AIM To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention.METHODS A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide(4NQO)to C57BL/6 mice.Moreover,we established a control group without 4NQO treatment of mice.Then,transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses,including low-grade IN(LGIN),high-grade IN(HGIN),and CA,and controlled normal tissue(NOR)samples.Differentially expressed genes(DEGs)were identified in the LGIN,HGIN,and CA groups,and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The CIBERSORT algorithm was used to detect the pattern of immune cell infilt-ration.Immunohistochemistry(IHC)was also conducted to validate our results.Finally,the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice.RESULTS Compared with those in the NOR group,a total of 681541,and 840 DEGs were obtained in the LGIN,HGIN,and CA groups,respectively.Using the intersection of the three sets of DEGs,we identified 86 genes as key genes involved in the development of ESCC.Enrichment analysis revealed that these genes were enriched mainly in the keratinization,epidermal cell differentiation,and interleukin(IL)-17 signaling pathways.CIBERSORT analysis revealed that,compared with those in the NOR group,M0 and M1 macrophages in the 4NQO group showed stronger infiltration,which was validated by IHC.Serum cytokine analysis revealed that,compared with those in the NOR group,IL-1βand IL-6 were upregulated,while IL-10 was downregulated in the LGIN,HGIN,and CA groups.Moreover,the expression of the representative key genes,such as S100a8 and Krt6b,was verified in external human samples,and the results of immunohistochemical staining were consistent with the findings in mice.CONCLUSION We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions.In addition,we found that macrophage infiltration and abnormal alterations in the levels of inflam-mation-associated cytokines,such as IL-1β,IL-6,and IL-10,in the peripheral blood may be closely associated with the development of ESCC.
文摘Colorectal cancer(CRC)is a prevalent malignant tumor,with the global new cases reaching 1.9316 million and deaths reaching 935,200 in 2022.In China,therewere 555,500 new cases of CRC,with an age-standardized incidence rate of 24.07 per 10million,and 286,200 deaths.China accounts for approximately 30%of new cases and deaths from CRC worldwide,with East Asia accounting for over 75%.Initially,CRC presents as local tumor growth,but it has the potential to spread to other body parts over time.Perineural infiltration(PNI)is a relatively less discussed route of diffusion,yet it plays a crucial role in the progression and prognosis of CRC.PNI often occurs alongside local lymph nodes and distant metastases,posing challenges for treatment and management.Clinical symptoms,radiographic findings,and histopathological examination can be used to diagnose PNI with skipmetastasis.Symptoms commonly include local pain,paresthesia,andmotor impairment.Imaging helps identify the mass’s location and relationship to nerves,whereas histopathological examination confirms the diagnosis.Treatment of PNI skipmetastases is similar to other CRC metastases,including surgical resection,chemotherapy,radiotherapy,and targeted therapy.Surgical resection is the primary therapeutic approach,but the wider range of metastasis in PNI skip transfer may limit its feasibility.In cases where surgical resection is not possible,chemotherapy,radiotherapy,and targeted therapy are used to control tumor metastasis.In conclusion,PNI skip metastases increase the risk of poor prognosis for CRC,requiring a comprehensive approach with multiple treatments to prevent disease progression.Early detection and treatment are vital to improving prognosis.
文摘Background: A major cause of cancer death worldwide is bladder cancer, which is the most common malignant tumor of the urinary tract. PAEP is a member of the kernel lipocalin superfamily whose members share relatively low sequence similarity but have highly conserved exon/intron structure and three-dimensional protein folding. Most lipocalins are clustered on the long arm of chromosome 9. The purpose of this study was to clarify the correlation between PAEP expression level and bladder cancer. Methods: In the TCGA database, we obtained clinical and RNA sequencing data of 431 BLCA patients, including 412 BLCA tissues and 19 normal bladder tissues in the study. Analyses of bioinformatics were conducted in this study to determine the role of PAEP in bladder cancer. A quantitative real-time PCR method was used to quantitate the gene expression profile. Additionally, the effect of PAEP on tumor immune infiltration and prognosis was analyzed. Results: PAEP was a poor prognostic biomarker of bladder cancer because it was significantly upregulated. bladder cancer patients with higher PAEP expression had poor outcomes. An AUC of 0.780 was calculated from the area under the ROC curve. PAEP was associated with T stage, pathologic stage, Histologic grade and Subtype of bladder cancer patients, and served as an independent predictor of overall survival in bladder cancer patients. Functional enrichment analysis revealed PAEP was obviously enriched in pathways connected with carcinogenesis and immunosuppression. The expression of PAEP was significantly associated with tumor immune cells and immune checkpoints according to ssGSEA and Spearman correlation analysis. Conclusions: In this study, we screened and detected a mRNA, PAEP is a prognostic and immune-related biomarker in BLCA, which may contribute to the early diagnosis and treatment of BLCA.
基金supported by the National Natural Science Foundation of China[No.81602020]the Tianjin Medical University Cancer Institute&Hospital Research Project[No.1805].
文摘Background:The molecular mechanism underlying the involvement of the Transferrin receptor(TFRC)in cervical cancer remains poorly understood.This study aims to elucidate the role of TFRC in cervical cancer by analyzing data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.Methods:TFRC protein expression was obtained from Human Protein Altas(HPA).All datas were collected from TCGA and GTEx.In this study,we analyzed the expression of TFRC in cervical cancer and its clinical significance.Through Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene set enrichment analyses(GSEA),investigated the related molecular pathways of TFRC.The relationship between TFRC and immune infiltration was then examined.The prognosis of different immune cell subsets was then analyzed after dividing cervical cancer patients into high and low expression of TFRC groups.Results:TFRC is highly expressed in various tumor tissues compared to control normal tissues,including cervical cancer.An increased expression of TFRC was associated with higher Tumor(T)and Node(N)stage,as well as a higher clinical stage.Kaplan–Meier(KM)survival analysis investigated that higher TFRC expression patients have a poor overall survival(OS),disease specific survival(DSS)and progress free interval(PFI).Both KEGG and GSEA enriched signaling pathway by high TFRC and low TFRC groups.There was a significant negative linear correlation between TFRC expression and immune infiltration.TFRC affects the prognosis of cervical cancer patients through immune pathway.Conclusions:Cervical cancer patients with TFRC expression may have a worse prognosis.
基金the Natural Science Foundation of Shaanxi Province(Youth Projectno.2021JQ-423)the foundation of the Second Affiliated Hospital of Xi'an Jiaotong University(no.RC(XM)201706)。
文摘Background:Owing to the occurrence of primary or secondary tolerance,the efficacy of immunotherapy for hepatocellular carcinoma(HCC)patients is limited.Therefore,the mechanism underlying this tolerance needs to be further investigated.B cell–specific Moloney murine leukemia virus integration site 1(BMI1)is associated with cancer stem cell tumorigenesis,progression,and the maintenance of the self-renewal.However,the effect of BMI1 expression on immune infiltration and prognosis in HCC is still unclear.Methods:To assess the relationship between BMI1 expression and HCC prognosis and immune infiltration,the GEPIA database,TIMER database,and K-M plotter were used.TIMER database was used to determine the levels ofBMI1 in various tumor tissues and corresponding normal tissues,and examine the association between BMI1 expression and tumor-infiltrating immune cells.GEPIA database was applied to determine BMI1 expression in various tumor tissues and corresponding normal tissues.K-M Plotter was used to study the relationships among BMI1 expression,clinicopathological features,and survival rates.Results:BMI1 expression was markedly higher in various solid tumors compared with that in the respective normal tissues,including HCC,and high expression led to poor relapse-free survival and overall survival in HCC patients.BMI1 overexpression was also correlated with the infiltration of immune cells(eg,B cells,CD8+T cells,CD4+T cells,dendritic cells,neutrophils,and macrophages)and positively associated with different subsets of T cells,monocytes,and M1 macrophages,among others.Conclusions:This study demonstrates that high BMI1 expression is strongly correlated with immune infiltration and poor prognosis in HCC.Increased expression of BMI1 might thus be a potential mechanism of immune tolerance in this disease.
基金the framework of the SWATCH project (Prima project) funded by the DGRSDT, Algeria
文摘Infiltration is an important part of the hydrological cycle, and it is one of the main abstractions accounted for in the rainfall-runoff modeling. The main purpose of this study is to compare the infiltration models that were used to assess the infiltration rate of the Mitidja Plain in Algeria. Field infiltration tests were conducted at 40 different sites using a double ring infiltrometer. Five statistical comparison criteria including root mean squared error(RMSE), normalized root mean squared error(NRMSE), coefficient of correlation(CC), Nash-Sutcliffe efficiency(NSE), and Kling-Gupta efficiency(KGE) were used to determine the best performing infiltration model and to confirm anomalies between predicted and observed values. Then we evaluated performance of five models(i.e., the Philip model, Kostiakov model, Modified Kostiakov model, Novel model, and Horton model) in simulating the infiltration process based on the adjusted performance parameters cited above. Results indicated that the Novel model had the best simulated water infiltration process in the Mitidja Plain in Algeria. However, the Philip model was the weakest to simulate the infiltration process. The conclusion of this study can be useful for estimating infiltration rate at various sites using a Novel model when measured infiltration data are not available and are useful for planning and managing water resources in the study area.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82060483)Guangxi Research Foundation for Science&Technology Base and Talent Special(Grant No.AD19110079)Natural Science Foundation of Guangxi Province(Grant No.2020GXNSFBA238002).
文摘Background:Cytochrome b561(CYB561)plays a critical role in neuroendocrine function,cardiovascular regulation,and tumor growth;however,the prognostic value of CYB561 in patients with breast cancer and the relationship between CYB561 expression and immune infiltration in breast cancer remain unclear.Methods:The mRNA expression and clinical data of patients with breast cancer were obtained from The Cancer Genome Atlas database.Functional enrichment analysis was used to explore underlying biological functions associated with CYB561.The methylation status of CYB561 was analyzed using the MethSurv database.The enrichment score of immune cell infiltration for CYB561 in breast cancer was calculated using single-sample gene set enrichment analysis.The prognostic value of CYB561 was evaluated using Kaplan-Meier method and Cox regression analysis.Based on the results of the multivariate Cox analysis,a nomogram was constructed to predict the effect of CYB561 expression on overall survival(OS).Results:The results showed that CYB561 was highly expressed in breast cancer tissues.Hypomethylation of CYB561 is associated with an unfavorable prognosis.In multivariate Cox regression analysis,CYB561 was an independent prognostic factor for OS.Functional enrichment analysis indicated that estrogen signaling pathway,inflammatory response,KRAS signaling pathway,epithelial-mesenchymal transition,leukocyte migration,and regulation of lymphocyte activation were strongly enriched in the low CYB561 expression group.Additionally,CYB561 expression was negatively correlated with immune infiltration of B cells,plasmacytoid dendritic cells,dendritic cells,and neutrophils.Conclusion:CYB561 may serve as a potential biomarker for breast cancer diagnosis and prognosis.
基金supported by the National Natural Science Foundation of China(51835005,52273237,51871103)National Key Research and Development Program of China(2020YFB2010401)+1 种基金the Hubei Province Natural Science Foundation for innovative research groups(2020CFA030)Tencent Foundation and the Independent Innovation Research Fund of Huazhong University of Science and Technology(2019kfyXMBZ025).
文摘The flexible pressure sensor has been credited for leading performance including higher sensitivity,faster response/recovery,wider detection range and higher mechanical durability,thus driving the development of novel sensing materials enabled by new processing technologies.Using atomic layer infiltration,Pt nanocrystals with dimensions on the order of a few nanometers can be infiltrated into the compressible lamellar structure of Ti3C2Tx MXene,allowing a modulation of its interlayer spacing,electrical conductivity and piezoresistive property.The flexible piezoresistive sensor is further developed from the Pt-infiltrated MXene on a paper substrate.It is demonstrated that Pt infiltration leads to a significant enhancement of the pressure-sensing performance of the sensor,including increase of sensitivity from 0.08 kPa^(-1)to 0.5 kPa^(-1),extension of detection limit from 5 kPa to 9 kPa,decrease of response time from 200 ms to 20 ms,and reduction of recovery time from 230 ms to 50 ms.The mechanical durability of the flexible sensor is also improved,with the piezoresistive performance stable over 1000 cycles of flexure fatigue.The atomic layer infiltration process offers new possibilities for the structure modification of MXene for advanced sensor applications.
文摘BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is a malignant tumor of the hepatobiliary system with concealed onset,strong invasiveness and poor prognosis.AIM To explore the disease characteristic genes that may be helpful in the diagnosis of ICC and affect immune cell infiltration.METHODS We downloaded two ICC-related human gene expression profiles from GEO database as the training group(GSE26566 and GSE32958 datasets)for difference analysis,and performed enrichment analysis on differential genes.The least absolute shrinkage and selection operator(LASSO),support vector machinerecursive feature elimination(SVM-RFE)and random forest(RF),three machine learning algorithms,were used to screen the characteristic genes.Double verification was carried out on GSE107943 and The Cancer Genome Atlas,two verification groups.Receiver operating characteristic curve and area under the curve(AUC)were used to evaluate the diagnostic efficacy of genes for ICC.CIBERSORT and ssGSEA algorithms were used to evaluate the effect of characteristic genes on immune infiltration pattern.Human Protein Atlas(HPA)was used to analyze the protein expression level of the target gene.RESULTS A total of 1091 differential genes were obtained in the training group.Enrichment analysis showed that the above genes were mainly enriched in small molecular catabolism,complement and coagulation cascade,bile secretion and other functions and pathways.Twentyfive characteristic genes were screened by LASSO regression,19 by SVM-RFE algorithm,and 30 by RF algorithm.Three algorithms were used in combination to determine the characteristic gene of ICC:MMP14.The verification group confirmed that the genes had a high diagnostic accuracy(AUC values of the training group and the verification group were 0.960,0.999,and 0.977,respectively).Comprehensive analysis of immune infiltration showed that MMP14 could affect the infiltration of monocytes,activated memory CD4 T cells,resting memory CD4 T cells,and other immune cells,and was closely related to the expression of CD200,cytotoxic T-lymphocyteassociated antigen 4,CD14,CD44,and other immune checkpoints.The results of immunohistochemistry in HPA database showed was indeed overexpressed in ICC.CONCLUSION MMP14 can be used as a disease characteristic gene of ICC,and may regulate the distribution of immune-infiltrating cells in the ICC tumor microenvironment,which provides a new method for the determination of ICC diagnostic markers and screening of therapeutic targets.
基金This study was supported by grants from the Central Guidance on Local Science and Technology Development Fund of HeBei Province(226Z7705G)Hebei Natural Science Foundation(H2020206458,H2020206513 and H2022206552)+1 种基金Science and Technology Research Project of Colleges and Universities in Hebei Province(ZD2021074 and ZD2022143)2022 Introduction of Foreign Intellectual Property Project in Hebei Province(SWZYCYZ202001).
文摘Hepatocellular carcinoma(HCC)is the most common fatal cancer worldwide,patients with HCC have a high mortality rate and poor prognosis.PANoptosis is a novel discovery of programmed cell death associated with cancer development.However,the role of PANoptosis in HCC remains obscure.In this study,we enrolled 274 PANoptosisrelated genes(PANRGs)and screened 8 genes to set up a prognostic model.A previous scoring system calculated PANscore was utilized to quantify the individual risk level of each HCC patient,and the reliability of the prognostic model has been validated in an external cohort.Nomogram constructed with PANscore and clinical characteristics were used to optimize individualized treatment for each patient.Single-cell analysis revealed a PANoptosis model associated with tumor immune cell infiltration,particularly natural killer(NK)cells.Further exploration of hub genes and assessment of the prognostic role of these 4 hub genes in HCC by quantitative real-time PCR(qRT-PCR)and immunohistochemistry(IHC).In conclusion,we evaluated a PANoptosis-based prognostic model as a potential prognostic biomarker for HCC patients.
基金Funded by the National Natural Science Foundation of China(Nos.52002003 and 52002098)Natural Science Foundation of Anhui Province,China(No.2008085QE196)Open Fund of Key Laboratory of Green Fabrication and Surface Technology of Advanced Metal Materials(Anhui University of Technology),Ministry of Education(No.GFST2020KF09)。
文摘ZrC_(x)-NbC_(y)-Cu composites were fabricated by pressure-less reactive infiltration of Zr-Cu binary melts into porous NbC preforms at 1300℃.The effect of Zr content in the infiltrator on microstructure of the as-synthesized composites was studied.Mechanical properties of the composites were reported.A partial displacement of Nb atoms in NbC by Zr atoms from Zr-Cu melt occurs during the reaction between Zr-Cu melt and porous NbC preform.The formation of a core-shell structure suggests the reaction is mainly a dissolutionprecipitation type.NbC dissolves into Zr-Cu melt,from which the(Nb,Zr)C_(z)phase precipitates and grows.With increasing Zr content in the Zr-Cu infiltrator,the reaction is enhanced and the infiltration is easily chocked.ZrC_(x)-NbC_(y)-Cu composite is synthesized using Zr_(14)Cu_(51)infiltrator.The flexural strength and fracture toughness of ZrC_(x)-NbC_(y)-Cu composite reach 637 MPa and 12.7 MPa·m^(1/2),respectively.And the improved toughness is probably attributed to residual Cu phase and plate-like Nb_(x)C_(y)phases.
基金supported by the National Clinical Research Center for Geriatric Diseases Found[NCRCG-PLAGH-2022011]。
文摘Objective Diffuse large B-cell lymphoma(DLBCL)is often associated with bone marrow infiltration,and 2-deoxy-2-(18F)fluorodeoxyglucose positron emission tomography/computed tomography(^(18)F-FDG PET/CT)has potential diagnostic significance for bone marrow infiltration in DLBCL.Methods A total of 102 patients diagnosed with DLBCL between September 2019 and August 2022 were included.Bone marrow biopsy and^(18)F-FDG PET/CT examinations were performed at the time of initial diagnosis.Kappa tests were used to evaluate the agreement of^(18)F-FDG PET/CT with the gold standard,and the imaging features of DLBCL bone marrow infiltration on PET/CT were described.Results The total detection rate of bone marrow infiltration was not significantly different between PET/CT and primary bone marrow biopsy(P=0.302)or between the two bone marrow biopsies(P=0.826).The sensitivity,specificity,and Youden index of PET/CT for the diagnosis of DLBCL bone marrow infiltration were 0.923(95%CI,0.759-0.979),0.934(95%CI,0.855-0.972),and 0.857,respectively.Conclusion^(18)F-FDG PET/CT has a comparable efficiency in the diagnosis of DLBCL bone marrow infiltration.PET/CT-guided bone marrow biopsy can reduce the misdiagnosis of DLBCL bone marrow infiltration.
基金supported by the National Natural Science Foundation of China(Grant Number[No.82071956])and the Clinical Research Plan of Shanghai Hospital Development Center(Grant Number[No.2020CR4065]).
文摘Glutamine metabolism(GM)plays an important role in tumor growth and proliferation.Skin cutaneous melanoma(SKCM)is a glutamine-dependent cancer.However,the molecular characteristics and action mechanism of GM on SKCM remain unclear.Therefore,we aimed to explore the effects of GM-related genes on survival,clinicopathological characteristics,and the tumor microenvironment in SKCM.In this study,682 SKCM samples were obtained from the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.Consensus clustering was used to classify SKCM samples into distinct subtypes based on 41 GM-related genes.Differences in survival,immune infiltration,clinical characteristics,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways as well as differentially expressed genes(DEGs)between subgroups were evaluated.A prognostic model was constructed according to prognostic DEGs.Differential analyses in survival,immune infiltration,tumor microenvironment(TME),tumor mutation burden(TMB),stemness,and drug sensitivity between risk groups were conducted.We identified two distinct GM-related subtypes on SKCM and found that GM-related gene alterations were associated with survival probability,clinical features,biological function,and immune infiltration.Then a risk model based on six DEGs(IL18,SEMA6A,PAEP,TNFRSF17,AIM2,and CXCL10)was constructed and validated for predicting overall survival in SKCM patients.The results showed that the risk score was negatively correlated with CD8+T cells,activated CD4+memory T cells,M1 macrophages,andγδT cells.The group with a low-risk score was accompanied by a better survival rate with higher TME scores and lower stemness index.Moreover,the group with high-and low-risk score had a significant difference with the sensitivity of 75 drugs(p<0.001).Overall,distinct subtypes in SKCM patients based on GM-related genes were identified and the risk model was constructed,which might contribute to prognosis prediction,guide clinical therapy,and develop novel therapeutic strategies.
基金Supported by National Natural Science Foundation of China,No.81971489Natural Science Foundation of Guangdong Province,No.2022A1515011122。
文摘BACKGROUND Gastric cancer(GC)is a malignant tumor with high morbidity and mortality.Expression of COL5A2 is significantly elevated in GC.Abnormal expression of noncoding RNAs(ncRNAs)have been found in GC,including microRNA(miRNA)and long noncoding RNA(lncRNA).Competing endogenous RNA network plays an important regulatory role in GC.However,its specific regulatory mechanism has not been elucidated.AIM To gain insight into the ncRNA regulatory mechanism and immune microenvironment related to COL5A2 in GC.METHODS RNA sequencing data and clinical information from The Cancer Genome Atlas data portal were used to analyze the expressions of COL5A2,miRNA and lncRNA related to the prognosis of GC.Cox regression analysis and Kyoto Encyclopedia of Genes and Genomes analysis were performed to assess the risk factors and relevant function of COL5A2.StarBase was used to predict the interaction of miRNA–lncRNA or miRNA–mRNA in GC.The relationship between COL5A2,miR-144-3p and ENTPD1-AS1 were verified by dual luciferase reporter assay.The association of COL5A2 with immune cell infiltration were analyzed using the Tumor Immune Estimation Resource database and single sample gene set enrichment analysis.The expression of COL5A2 and macrophages in paired GC tissues were detected by immunohistochemical staining.RESULTS We verified that the upregulation of COL5A2 expression was associated with the prognosis of GC and was an independent risk factor for GC.miR-144-3p was downregulated and correlated with the prognosis of GC.miR-144-3p regulated the expression of COL5A2 through direct interaction with COL5A2.ENTPD1-AS1 was elevated in GC and competitively bound to miR-144-3p,thus inhibiting the expression of miR-144-3p.ENTPD1-AS1 enhanced the expression of COL5A2 through sponging miR-144-3p.Compared to paired normal tissue,COL5A2 expression was upregulated at the protein level,especially in the middle and late stages of GC.The high expression of COL5A2 was positively linked to macrophage infiltration in GC.CONCLUSION COL5A2 regulated by ENTPD1-AS1–miR-144-3p was associated with poor prognosis and macrophage infiltration in GC.This could be a new biomarker and therapeutic target in GC.
基金National Natural Science Foundation of China (81573959)Capital Health Development Research Special Project (2020-2-4193)。
文摘Objective:Constructing a prognostic model for gastric cancer(GC)based on cuproptosisrelated LncRNAs(CRLs)and predict the traditional Chinese medicine that regulate cuproptosis-related genes(CRGs).Methods:Clinical data and RNA-seq of 443 GC cases were obtained from The Cancer Genome Atlas(TCGA)database,and CRLs were screened by Pearson analysis,Cox regression,and least absolute shrinkage and selection operator(LASSO)regression to construct a risk model to predict GC prognosis,and the nomogram was constructed by combining risk scores and clinical characteristics.The accuracy of the model was validated by the receiver operating characteristic curve,Kaplan-Meier curves and C-index.To assess the correlation of risk scores with immune infiltration,immune checkpoint gene expression and chemotherapy/targeted agents.The Coremine Medical database was applied to predict potential traditional Chinese medicine that regulate CRGs.Results:Risk models for GC were constructed based on the risk scores of seven CRLs(AP001107.9,VCAN-AS1,AC016394.2,LINC02675,AC100814.1,HAGLR,and LINC01094).The AUC of the risk model predicting 1-,3-,and 5-year survival in GC patients was 0.720,0.682,and 0.711,and its prognostic value was better than age,Grade classification,and TNM stage.The AUC of the risk model combining age and TNM stage to predict 1-year survival in GC patients was 0.793.The risk score correlated with the degree of enrichment of immune cells such as tumorinfiltrating lymphocytes and regulatory T cells and the expression of 22 immune checkpoint genes such as LAG3,ICOS,CD28,NRP1 and the sensitivity of 13 chemotherapeutic/targeted agents.There are 58 traditional Chinese medicine with potential regulatory effects on CRGs,mainly for clearing heat and detoxing,promoting blood circulation and relieving pain,which are mainly attributed to the liver,spleen and lung meridians.Spirulina and osthole have potential regulatory effects on FDX1,a key gene in the death mechanism of cuproptosis.Conclusions:A risk signature constructed based on seven CRLs could assess the prognosis and immunity of GC,and Spirulina and Serpentine may have important regulatory efficacy on the mechanism of copper cuproptosis.