Effects of grassland vegetation roots on soil infiltration rate in Xiazangtan super large scale landslide distribution area in the upper reaches of the Yellow River,China

In order to study the infiltration characteristics of grassland soil in the super large scale landslides distribution area in the upper reaches of the Yellow River,this study selected the Xiazangtan super large scale distribution area in Jianzha County as the study area.Through experiments and numerical simulations,plant roots characteristics,soil physical properties and infiltration characteristics of naturally grazed grassland and enclosed grassland with different slope directions were compared and analyzed,and the influence of rainfall on seepage field and stability of the two grassland slopes were discussed.The results show that the highest soil moisture infiltration capacity(FIR)is found on the shady slope of the enclosed grassland(2.25),followed by the sunny slope of the enclosed grassland(1.23)and the shady slope of the naturally grazed grassland(-0.87).Correlation analysis show that soil water content,root dry weight density,total soil porosity,number of forks and root length are positively correlated with infiltration rate(P<0.05),whereas soil dry density is negatively correlated with infiltration rate(P<0.05).The results of stepwise regression analyses show that soil water content,total soil porosity,root length and number of forks are the main factors affecting soil infiltration capacity.And the ability of roots to increase soil infiltration by improving soil properties is higher than the effect of roots itself.After 60 min of simulated rainfall,the safety factors of the shady slopes of naturally grazed grassland and enclosed grassland are reduced by 29.56%and 19.63%,respectively,comparing to those before rainfall.Therefore,in this study,the roots play a crucial role in regulating soil infiltration and enhance slope stability by increasing soil water content,soil total porosity and shear strength while decreasing soil dry density.The results of this study provide theoretical evidence and practical guidance for the effective prevention and control of secondary geological disasters such as soil erosion and shallow landslide on the slope of river banks in the study area by using plant ecological measures.

Ablation properties of C/C composites with various needled preforms prepared by isothermal chemical vapor infiltration

The ablation properties of C/C composites with four different needled preforms prepared by isothermal chemical vapor infiltration （ICVI）, which are super-thin mat lay-up, 0°/90° weftless fabric lay-up, 0°/45° weftless fabric lay-up and 0°/45° twill fabric lay-up, were quantitatively evaluated by performing the ablation tests with an engine torch. And their ablation discrepancies were analyzed according to the surface characteristic, porosity and thermal diffusivity. The results show that the 0°/45° weftless composite has a fiat eroded surface with no obvious macroscopic pits. Its thickness and mass erosion rates are decreased by about 46.8% and 34.8%, 25.0% and 27.5%, and 17.5% and 19.4% compared with those of the mat, the 0°/90° weftless and the 0°/45° twill composites, respectively. The ablation properties are mainly controlled by the thermo-chemical effect （oxidation）, and a little by the thermo-mechanical effect （mechanical denudation）. The needling fiber bundles play an important role in accelerating the ablation process and resulting in the heterogeneous ablation.

A Numerical Study of Densification Behavior of Silicon Carbide Matrix Composites in Isothermal Chemical Vapor Infiltration

We studied the characteristics of two-scale pore structure of preform in the deposition process and the mass transfer of reactant gas in dual-scale pores, and observed the physiochemical phenomenon associated with the reaction. Thereby, we established mathematical models on two scales, respectively, preform and reactor. These models were used for the numerical simulation of the process of ceramic matrix composites densified by isothermal chemical vapor infiltration(ICVI). The models were used to carry out a systematic study on the influence of process conditions and the preform structure on the densification behaviors. The most important findings of our study are that the processing time could be reduced by about 50% without compromising the quality of the material, if the processing temperature is 950-1 000 ℃ for the first 70 hours and then raised to 1 100 ℃.

Gastric infiltration of diffuse large B-cell lymphoma: Endoscopic diagnosis and improvement of lesions after chemotherapy

Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of the non-Hodgkin’s lymphoma (NHL) accounting for about 40% of all NHLs. This is a case report about the endoscopic appearance of a DLBCL with infiltration to the stomach in a 39-year-old female. She had a 6-mo history of lumbar and left upper quadrant pain with intermittent episodes of melena. A computer tomograghy (CT) scan showed mural thickening of the gastric antrum. Endoscopic examination revealed multiple gastric ulcers. Definite diagnosis could be made by endoscopic biopsies and the patient had a good response to chemotherapy. This response correlated well with a further endoscopic follow-up. A follow-up endoscopic examination could be considered to evaluate a good response to chemotherapy in DLBCL patients with secondary gastric dissemination.

A prognosis model for predicting immunotherapy response of esophageal cancer based on oxidative stress-related signatures

Oxidative stress(OS)is intimately associated with tumorigenesis and has been considered a potential therapeutic strategy.However,the OS-associated therapeutic target for esophageal squamous cell carcinoma(ESCC)remains unconfirmed.In our study,gene expression data of ESCC and clinical information from public databases were downloaded.Through LASSO-Cox regression analysis,a risk score(RS)signature map of prognosis was constructed and performed external verification with the GSE53625 cohort.The ESTIMATE,xCell,CIBERSORT,TIMER,and ImmuCellAI algorithms were employed to analyze infiltrating immune cells and generate an immune microenvironment(IM).Afterward,functional enrichment analysis clarified the underlying mechanism of the model.Nomogram was utilized for forecasting the survival rate of individual ESCC cases.As a result,we successfully constructed an OS-related genes(OSRGs)model and found that the survival rate of high-risk groups was lower than that of low-risk groups.The AUC of the ROC verified the strong prediction performance of the signal in these two cohorts further.According to independent prognostic analysis,the RS was identified as an independent risk factor for ESCC.The nomogram and follow-up data revealed that the RS possesses favorable predictive value for the prognosis of ESCC patients.qRT-PCR detection demonstrated increased expression of MPC1,COX6C,CYB5R3,CASP7,and CYCS in esophageal cancer patients.In conclusion,we have constructed an OSRGs model for ESCC to predict patients’prognosis,offering a novel insight into the potential application of the OSRGs model in ESCC.

Effect of slope angle on fractured rock masses under combined influence of variable rainfall infiltration and excavation unloading

Intense precipitation infiltration and intricate excavation processes are crucial factors that impact the stability and security of towering and steep rock slopes within mining sites.The primary aim of this research was to investigate the progression of cumulative failure within a cracked rock formation,considering the combined effects of precipitation and excavation activities.The study was conducted in the Huangniuqian eastern mining area of the Dexing Copper Mine in Jiangxi Province,China.An engineering geological investigation was conducted,a physical model experiment was performed,numerical calculations and theoretical analysis were conducted using the matrix discrete element method(Mat-DEM),and the deformation characteristics and the effect of the slope angle of a fractured rock mass under different scenarios were examined.The failure and instability mechanisms of the fractured rock mass under three slope angle models were analyzed.The experimental results indicate that as the slope angle increases,the combined effect of rainfall infiltration and excavation unloading is reduced.A novel approach to simulating unsaturated seepage in a rock mass,based on the van Genuchten model(VGM),has been developed.Compared to the vertical displacement observed in a similar physical experiment,the average relative errors associated with the slope angles of 45,50,and 55were 2.094%,1.916%,and 2.328%,respectively.Accordingly,the combined effect of rainfall and excavation was determined using the proposed method.Moreover,the accuracy of the numerical simulation was validated.The findings contribute to the seepage field in a meaningful way,offering insight that can inform and enhance existing methods and theories for research on the underlying mechanism of ultra-high and steep rock slope instability,which can inform the development of more effective risk management strategies.

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.

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.

Discussion on the Infiltration of Experiential Career Education Concept in Biology Teaching in Senior High Schools

Based on the implementation of the new college entrance examination reform policy and the demand of related policies,the choice of subjects for high school students has shifted from the traditional relatively single model of arts and sciences division to the"3+3"model,and the topic of"how to infiltrate the concept of career education in the teaching process of senior high schools"has become increasingly important.However,at present,the implementation of career education in senior high schools is frequently limited,mainly in the form of class meetings,which instills the concept of career education to students.Therefore,the implementation effect is often not satisfactory.Therefore,experiential learning,a novel and efficient learning method,has entered public's view.Based on relevant research literature at home and abroad,we started with the importance and urgency of implementing career education in high schools,and generally reviewed the research status and future development trends of experiential career education both domestically and internationally.The practical and theoretical significance of the research were explained,and relevant concepts were summarized.Finally,strategic suggestions were proposed for integrating experiential career education concepts into biology teaching in ordinary high schools in China.

Research on the Effective Infiltration of Ecological Aesthetic Education in Business English Teaching From the Perspective of Curriculum-Based Political and Virtuous Awareness Education

Ecological aesthetic education is a fusion of aesthetic education,environmental education,and ecological aesthetics research.The product of this combination is an ecological paradigm of Chinese aesthetic education research.Based on a holistic ecological view,ecological aesthetic education elevates it as an aesthetic principle to achieve the value position of ecological aesthetics in people’s lives and finally realizes the poetic habitation of human beings on the earth through the eco-aesthetic practice.This paper firstly introduces the background of China’s curriculum-based political and virtuous awareness(CPVA)education and its relevance to ecological aesthetic education in business English teaching which necessitate the infiltration of eco-aesthetic education in business English teaching.Then,with the teaching practice of Integrated Business English course,this paper explores the three aspects of how to effectively infiltrate ecological aesthetic education in business English teaching.

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.

The Application of "Infiltration" Intercultural Communication Teaching in English Intensive Reading Teaching

Due to the general promotion of the new English curriculum standards,the training of students'intercultural communication skills has become the main goal of the current English teaching reform.In English teaching,reading teaching includes all aspects of English country customs,human accidents,political diplomacy,etc.The intensive reading of English reading helps students to understand the culture of English-speaking countries.Therefore,in order to improve the quality of English intensive reading in China,starting from the important role and main principles of"infiltration"intercultural communication teaching in English intensive reading teaching,to explore the application of"infiltration"cross-cultural communication teaching in English intensive reading teaching.

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.

Spatial-temporal heterogeneity and controlling factors of evapotranspiration in Nujiang River Basin based on Variable Infiltration Capacity(VIC)model

Land surface evapotranspiration(ET)is a critical component in the hydrological cycle but has not well been understood in data-scarce areas especially in river basins,like Nujiang River(NRB)which is characterized by large elevation gradient and different vegetation zones with complex processes of water and energy exchange.The quality of ET from optical remote sensing is constrained by cloud cover which is common in the NRB in the monsoon seasons.To understand factors controlling the spatial-temporal heterogeneity of ET in NRB,we employed the Variable Infiltration Capacity(VIC)hydrological model by parameter optimization with support of quality controlled remote sensing ET product and observed river runoff series in the river.The modeled ET has increased during 1984-2018,which might be one of the reasons for the runoff decrease but precipitation increase in the same period.ET increase and runoff decrease tended to be quicker within altitudinal band of 2000-4000 m than in other areas in NRB.We observed that ET variation in different climatic zones were controlled by different factors.ET is generally positively correlated with precipitation,temperature,and shortwave radiation but negatively with relative humidity.In the Tundra Climate(Et)zone in the upper reach of NRB,ET is controlled by precipitation,while it is controlled by shortwave radiation in the snow climate with dry winter(Dw)zone.ET increase is influenced by the increase of temperature,wind speed,and shortwave radiation in the middle and downstream of NRB with warm temperate climate,fully humid(Cf)and warm temperate climate with dry winter(Cw).

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.

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.

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.

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.

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.

Polo-like kinase 1 as a biomarker predicts the prognosis and immunotherapy of breast invasive carcinoma patients

Invasive breast carcinoma(BRCA)is associated with poor prognosis and high risk of mortality.Therefore,it is critical to identify novel biomarkers for the prognostic assessment of BRCA.Methods:The expression data of polo-like kinase 1(PLK1)in BRCA and the corresponding clinical information were extracted from TCGA and GEO databases.PLK1 expression was validated in diverse breast cancer cell lines by quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting.Single sample gene set enrichment analysis(ssGSEA)was performed to evaluate immune infiltration in the BRCA microenvironment,and the random forest(RF)and support vector machine(SVM)algorithms were used to screen for the hub infiltrating cells and calculate the immunophenoscore(IPS).The RF algorithm and COX regression model were applied to calculate survival risk scores based on the PLK1 expression and immune cell infiltration.Finally,a prognostic nomogram was constructed with the risk score and pathological stage,and its clinical potential was evaluated by plotting calibration charts and DCA curves.The application of the nomogram was further validated in an immunotherapy cohort.Results:PLK1 expression was significantly higher in the tumor samples in TCGA-BRCA cohort.Furthermore,PLK1 expression level,age and stage were identified as independent prognostic factors of BRCA.While the IPS was unaffected by PLK1 expression,the TMB and MATH scores were higher in the PLK1-high group,and the TIDE scores were higher for the PLK1-low patients.We also identified 6 immune cell types with high infiltration,along with 11 immune cell types with low infiltration in the PLK1-high tumors.A risk score was devised using PLK1 expression and hub immune cells,which predicted the prognosis of BRCA patients.In addition,a nomogram was constructed based on the risk score and pathological staging,and showed good predictive performance.Conclusions:PLK1 expression and immune cell infiltration can predict post-immunotherapy prognosis of BRCA patients.