Metadherin promotes stem cell phenotypes and correlated with immune infiltration in hepatocellular carcinoma

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.

Surrogate modeling for unsaturated infiltration via the physics and equality-constrained artificial neural networks

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.

SOX11 as a potential prognostic biomarker in hepatocellular carcinoma linked to immune infiltration and ferroptosis

Objective:SOX11 is expressed in numerous malignancies,including hepatocellular carcinomas(HCC),but its oncogenic function has not been elucidated.Here,we performed a comprehensive bioinformatics analysis of the Liver Hepatocellular Carcinoma(LIHC)dataset to investigate the function of SOX11 in tumorgenesis.Methods:SOX11 expression data from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)were validated by immunohistochemistry(IHC).Co-expression,differential expression,and functional analyses utilized TCGA-LIHC,Timer 2.0,Metascape,GTEx,and LinkedOmics databases.Associations with immune infiltration,ferroptosis,and immune checkpoint genes were assessed.Genetic changes were explored via CBioPortal.Logistic regression,receiver operating characteristic curve(ROC),Kaplan-Meier analysis,and nomogram modeling evaluated associations with HCC clinicopathological features.SOX11’s impact on proliferation and migration was studied in HepG2 and HuH7 cell lines.Results:SOX11 was significantly elevated in HCC tumors compared to controls.SOX11-associated genes exhibited differential expression in pathways involving extracellular membrane ion channels.Significant associations were found between SOX11 levels,immune infiltration,ferroptosis,and immune checkpoint genes in HCC tissue.SOX11 levels correlated with HCC stage,histologic grade,and tumor status,and independently predicted overall and disease-specific survival.SOX11 expression effectively distinguished between tumor and normal liver tissue.Spearman correlations highlighted a significant relationship between SOX11 and ferroptosis-associated genes.Decreased SOX11 levels in HepG2 and HuH7 cells resulted in reduced proliferation and migration.Conclusions:SOX11 was found to represent a promising biomarker within HCC diagnosis and prognosis together with being a possible drug-target.

CRABP2 regulates infiltration of cancer-associated fibroblasts and immune response in melanoma

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.

A Prognostic Biomarker for Bladder Cancer Correlated with Immune Infiltration Is PAEP

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.

Effects of diamond particle size on microstructure and properties of diamond/Al-12Si composites prepared by vacuum-assisted pressure infiltration

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.

Microstructure and Oxidation Behavior of ZrB_(2)-SiC Ceramics Fabricated by Tape Casting and Reactive Melt Infiltration

ZrB_(2)-based ceramics typically necessitate high temperature and pressure for sintering,whereas ZrB_(2)-SiC ceramics can be fabricated at 1500℃using the process of reactive melt infiltration with Si.In comparison to the conventional preparation method,reactive synthesis allows for the more facile production of ultra-high temperature ceramics with fine particle size and homogeneous composition.In this work,ZrSi_(2),B4C,and C were used as raw materials to prepare ZrB_(2)-SiC via combination of tape casting and reactive melt infiltration herein referred to as ZBC ceramics.Control sample of ZrB_(2)-SiC was also prepared using ZrB_(2) and SiC as raw materials through an identical process designated as ZS ceramics.Microscopic analysis of both ceramic groups revealed smaller and more uniformly distributed particles of the ZrB_(2) phase in ZBC ceramics compared to the larger particles in ZS ceramics.Both sets of ceramics underwent cyclic oxidation testing in the air at 1600℃for a cumulative duration of 5 cycles,each cycle lasting 2 h.Analysis of the oxidation behavior showed that both ZBC ceramics and ZS ceramics developed a glassy SiO_(2)-ZrO_(2) oxide layer on their surfaces during the oxidation.This layer severed as a barrier against oxygen.In ZBC ceramics,ZrO_(2) is finely distributed in SiO_(2),whereas in ZS ceramics,larger ZrO_(2) particles coexist with glassy SiO_(2).The surface oxide layer of ZBC ceramics maintains a dense structure because the well-dispersed ZrO_(2) increases the viscosity of glassy SiO_(2),preventing its crystallization during the cooling.Conversely,some SiO_(2) in the oxide layer of ZS ceramics may crystallize and form a eutectic with ZrO_(2),leading to the formation of ZrSiO_(4).This leads to cracking of the oxide layer due to differences in thermal expansion coefficients,weakening its barrier effect.An analysis of the oxidation resistance shows that ZBC ceramics exhibit less increase in oxide layer thickness and mass compared to ZS ceramics,suggesting superior oxidation resistance of ZBC ceramics.

Infiltration,runoff,and slope stability behaviors of infinite slope with macropores based on an improved Green–Ampt model

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.

Ablation behaviour and mechanical performance of ZrB_(2)-ZrC-SiC modified carbon/carbon composites prepared by vacuum infiltration combined with reactive melt infiltration

The development of advanced aircraft relies on high performance thermal-structural materials,and carbon/carbon com-posites(C/C)composited with ultrahigh-temperature ceramics are ideal candidates.However,the traditional routes of compositing are either inefficient and expensive or lead to a non-uniform distribution of ceramics in the matrix.Compared with the traditional C/C-ZrC-SiC composites prepared by the reactive melt infiltration of ZrSi_(2),C/C-ZrB_(2)-ZrC-SiC composites prepared by the vacuum infiltration of ZrB_(2) combined with reactive melt infiltration have the higher content and more uniform distribution of the introduced ceramic phases.The mass and linear ablation rates of the C/C-ZrB_(2)-ZrC-SiC composites were respectively 68.9%and 29.7%lower than those of C/C-ZrC-SiC composites prepared by reactive melt infiltration.The ablation performance was improved because the volatilization of B_(2)O_(3),removes some of the heat,and the more uniformly distributed ZrO_(2),that helps produce a ZrO2-SiO2 continu-ous protective layer,hinders oxygen infiltration and decreases ablation.

BMI1 overexpression is correlated with a poor prognosis and immune infiltration in hepatocellular carcinoma

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.

Current status of nerve infiltration by skip metastases in colorectal cancer

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.

Transcriptome sequencing reveals novel biomarkers and immune cell infiltration in esophageal tumorigenesis

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.

Screening and immune infiltration analysis of ferroptosis-related genes in pancreatic cancer with predictions for traditional Chinese medicine treatments

Background:This study aims to explore the involvement of ferroptosis-related genes and pathogenesis in pancreatic cancer and predict potential therapeutic interventions using Traditional Chinese Medicine(TCM).Methods:We utilized gene expression datasets,ferroptosis upregulated genes and applied machine learning algorithms,including LASSO and SVM-RFE,to identify key ferroptosis-related genes in pancreatic cancer.Perform Gene Ontology,Kyoto Encyclopedia of Genes and Genomes,and Disease Ontology enrichment analysis,immune infiltration analysis and correlation analysis between immune infiltrating cells and characteristic genes on differentially expressed genes using the R software package.Retrieve potential traditional Chinese medicine for targeted ferroptosis gene therapy for pancreatic cancer through Coremine and Herb databases.Results:Seventeen feature genes were identified,with significant implications for immune cell infiltration in pancreatic cancer.The results of immune cell infiltration analysis showed that B cells naive,B cells memory,T cells regulatory,and M0 macrophages were significantly upregulated in pancreatic cancer patients;Mast cells resting were significantly downregulated.Chinese herbal medicines such as ginkgo,turmeric,ginseng,Codonopsis pilosula,Zedoary turmeric,deer tendons,senna leaves,Guanmu Tong,Huangqi,and Banzhilian are potential drugs for targeted ferroptosis gene therapy for pancreatic cancer.Conclusion:TIMP1 emerged as a key gene,with several TCM herbs predicted to modulate its expression,offering new avenues for treatment.

Effects of Typical Soil and Stratification Thickness on Water Infiltration Characteristics in Central Ningxia

In order to compare the influence of different soil types and stratification on water infiltration capacity,two main types of soil in the desert steppe,sierozem(S)and aeolian sandy soil(A),were selected,and infiltration simulation tests were conducted on homogeneous soil and layered soil(layer thickness 5,10,and 20 cm),respectively.The results show that during the whole experiment,there was a small difference between S5A95(aeolian sandy soil 95 cm thick was covered with sierozem 5 cm thick)and S10A90(aeolian sandy soil 90 cm thick was covered with sierozem 10 cm thick)in the wetting front process,infiltration rate and cumulative infiltration,but there was a significant difference between S5A95 and S20A80(aeolian sandy soil 80 cm thick was covered with sierozem 20 cm thick).In the initial infiltration stage,there was no significant difference between A5S95(sierozem 95 cm thick was covered with aeolian sandy soil 5 cm thick)and A10S90(sierozem 90 cm thick was covered with aeolian sandy soil 10 cm thick).However,with the increase of infiltration time,the wetting front process,A5S95,A10S90 and A20S80 had significant differences in terms of wetting front process,infiltration rate and cumulative infiltration.The infiltration capacity of A was significantly higher than that of S.Combined with linear R 2 value and model parameters,the three infiltration models were comprehensively compared,and the fitting process and results of the general empirical model for the infiltration process of homogeneous soil and layered soil showed good results.Three models were used to simulate the water infiltration process of layered soil with different textures,and the order of the effect is as follows:general empirical model>Kostiakov model>Philip model.Soil type and layer thickness had a great influence on water infiltration process.When sierozem was covered with aeolian sandy soil 20 cm thick,the infiltration capacity was the best.As aeolian sandy soil was covered with sierozem 10 cm thick,the infiltration effect was the worst.Therefore,once coarse graying occurs on the surface of sierozem(the thickness of sand is more than 20 cm)or when the content of fine particles overlying aeolian sandy soil(the thickness of silt and clay soil is more than 10 cm)during ecological restoration is high,the soil hydrological characteristics will change significantly,which may lead to changes in vegetation types and even ecosystem structure.

Cervical cancer with transferrin receptor has a poor prognosis and is associated with immune infiltration, according to a comprehensive bioinformatics study

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.

Comprehensive bioinformatics analysis of CYB561 expression in breast cancer:Link between prognosis and immune infiltration

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.

MXene-based flexible pressure sensor with piezoresistive properties significantly enhanced by atomic layer infiltration

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.

Estimation and inter-comparison of infiltration models in the agricultural area of the Mitidja Plain, Algeria

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.

Construction of the panoptosis-related gene model and characterization of tumor microenvironment infiltration in hepatocellular carcinoma

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.

Characterization of prognosis and immune infiltration by a novel glutamine metabolism-related model in cutaneous melanoma

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.