Wear Performance of Ni/ZrO_2 Infiltrated Composite Layer

The Ni/ZrO2 was used as raw materials to fabricate the surface infiltrated composite layer with 1-4 mm thickness on cast steel substrate through vacuum infiltrated casting technology. The microstructure indicated that the infiltrated composite layer included surface composite layer and transition layer. Wear property was investigated under room temperature and 450 ~C. The results indicated that the abrasion volume of substrate was 8 times that of the infiltrated composite layer at room temperature. The friction coefficient of infiltrated composite layer decreased with the increasing load. The wear resistance of infiltrated composite layer with different ZrO2 contents had been improved obviously under high temperature. The friction coefficient of infiltrated composite layer was decreased comparing with that at room temperature. The oxidation, abrasive and fatigue abrasion was the main wear mechanism at room temperature. Oxidation abrasion, fatigue wear and adhesive wear dominated the wearin~ process under elevated temperature.

Picosecond Laser Machining of Deep Holes in Silicon Infiltrated Silicon Carbide Ceramics

Silicon infiltrated silicon carbide （Si-SiC） ceramics, as high hardness materials, are difficult to machine, especially drilling micro-holes. In this study, the interaction of picosecond laser pulses （1 ps at 1 030 nm） with Si-SiC ceramics was investigated. Variations of the diameter and depth of circular holes with the growth of the laser energy density were obtained. The results indicate that the increase of machining depth follows a nonlinear relation with the increasing of laser energy density, while the diameter has little change with that. Moreover, it is found that some debris and particles are deposited around and inside the holes and waviness is in the entrance and at walls of the holes after laser processing.

Pressure infiltrated Cu/diamond composites for LED applications

Diamond reinforced copper （Cu/diamond） composites were prepared by a pressure infilla＇ation technique. The composites show a super high conductivity of 713 W.m-1.K-1 in combination with an extremely low coefficient of thermal expansion （CTE） of 7.72 × 10-6 K-1 （25-100℃）, which are achieved by modifying the copper matrix with adding 0.3 wt.% of boron to get a good thermal contact between the matrix and the diamond particles. By adopting a series of postmachining techniques the composites were made into near-net-shape parts, and an electroless silver coating was also successfully plated on the composites. Finally, their potential applications in the thermal management of fight emitting diodes （LED） were illustrated via prototype examples.

Electrochemical performance and stability of Sr-doped LaMnO_(3)-infiltrated yttria stabilized zirconia oxygen electrode for reversible solid oxide fuel cells

Porous Sr-doped lanthanum manganite–yttria stabilized zirconia(LSM–YSZ)oxygen electrode is prepared by an infiltration process for a reversible solid oxide fuel cell(RSOFC).X-ray diffraction and SEM analysis display that perovskite phase LSM submicro particles are evenly distributed in the porous YSZ matrix.Polarization curves and electrochemical impedance spectra are conducted for the RSOFC at 800 and 850C under both SOFC and SOEC modes.At 850℃,the single cell has the maximum power density of~726 mW/cm^(2)under SOFC mode,and electrolysis voltage of 1.35 V at 1 A/cm^(2)under SOEC mode.Fuel cell/water electrolysis cycle shows the cell has good performance stability during 6 cycles,which exhibits the LSM–YSZ oxygen electrode has high electrochemical performance and good stability.The results suggest that netw ork-like LSM–YSZ electrode made by infiltration process could be a promising oxygen electrode for high temperature RSOFCs.

LSM-infiltrated LSCF cathodes for solid oxide fuel cells

Mixed ionic-electronic conductors in the family of LaxSr1-xCoyFe1-y O3-δ have been widely studied as cathode materials for solid oxide fuel cells （SOFCs）. However, the long-term stability was a concern. Here we report our findings on the effect of a thin film coating of La0.85Sr0.15MnO3-δ （LSM） on the performance of a porous La0.6Sr0.4Co0.2Feo.8O3-δ（LSCF） cathode. When the thicknesses of the LSM coatings are appropriate, an LSM-coated LSCF electrode showed better stability and lower polarization （or higher activity） than the blank LSCF cathode without LSM infiltration. An anode-supported cell with an LSM-infiltrated LSCF cathode demonstrated at 825 ℃ a peak power density of -1.07 W/cm2, about 24% higher than that of the same cell without LSM infiltration （-0.86 W/cm2）. Further, the LSM coating enhanced the stability of the electrode; there was little degradation in performance for the cell with an LSM-infiltrated LSCF cathode during 100 h operation.

NAD+associated genes as potential biomarkers for predicting the prognosis of gastric cancer

Nicotinamide adenine dinucleotide(NAD+)plays an essential role in cellular metabolism,mitochondrial homeostasis,inflammation,and senescence.However,the role of NAD+-regulated genes,including coding and long non-coding genes in cancer development is poorly understood.We constructed a prediction model based on the expression level of NAD+metabolism-related genes(NMRGs).Furthermore,we validated the expression of NMRGs in gastric cancer(GC)tissues and cell lines;additionally,β-nicotinamide mononucleotide(NMN),a precursor of NAD+,was used to treat the GC cell lines to analyze its effects on the expression level of NMRGs lncRNAs and cellular proliferation,cell cycle,apoptosis,and senescence-associated secretory phenotype(SASP).A total of 13 NMRGs-related lncRNAs were selected to construct prognostic risk signatures,and patients with high-risk scores had a poor prognosis.Some immune checkpoint genes were upregulated in the high-risk group.In addition,cell cycle,epigenetics,and senescence were significantly downregulated in the high-risk group.Notably,we found that the levels of immune cell infiltration,including CD8 T cells,CD4 naïve T cells,CD4 memory-activated T cells,B memory cells,and naïve B cells,were significantly associated with risk scores.Furthermore,the treatment of NMN showed increased proliferation of AGS and MKN45 cells.In addition,the expression of SASP factors(IL6,IL8,IL10,TGF-β,and TNF-α)was significantly decreased after NMN treatment.We conclude that the lncRNAs associated with NAD+metabolism can potentially be used as biomarkers for predicting clinical outcomes of GC patients.

PHLDA2 reshapes the immune microenvironment and induces drug resistance in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable prognosis.The dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment failure.The elucidation of PHLDA2’s involvement in HCC is imperative,and the clinical value of PHLDA2 is also underestimated.Here,bioinformatics analysis was performed in multiple cohorts to explore the phenotype and mechanism through which PHLDA2 may affect the progression of HCC.Then,the expression and function of PHLDA2 were examined via the qRT-PCR,Western Blot,and MTT assays.Our findings indicate a substantial upregulation of PHLDA2 in HCC,correlated with a poorer prognosis.The methylation levels of PHLDA2 were found to be lower in HCC tissues compared to normal liver tissues.Besides,noteworthy associations were observed between PHLDA2 expression and immune infiltration in HCC.In addition,PHLDA2 upregulation is closely associated with stemness features and immunotherapy or chemotherapy resistance in HCC.In vitro experiments showed that sorafenib or cisplatin significantly up-regulated PHLDA2 mRNA levels,and PHLDA2 knockdown markedly decreased the sensitivity of HCC cells to chemotherapy drugs.Meanwhile,we found that TGF-βinduced the expression of PHLDA2 in vitro.The GSEA and in vitro experiment indicated that PHLDA2 may promote the HCC progression via activating the AKT signaling pathway.Our study revealed the novel role of PHLDA2 as an independent prognostic factor,which plays an essential role in TME remodeling and treatment resistance in HCC.

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.

IQGAP3 promotes the progression of glioma as an immune and prognostic marker

Background:IQGAP3 plays a crucial role in regulating cell proliferation,division,and cytoskeletal organization.Abnormal expression of IQGAP3 has been linked to various tumors,but its function in glioma is not well understood.Methods:Various methods,including genetic differential analysis,single-cell analysis,ROC curve analysis,Cox regression,Kaplan-Meier analysis,and enrichment analysis,were employed to analyze the expression patterns,diagnostic potential,prognostic implications,and biological processes involving IQGAP3 in normal and tumor tissues.The impact of IQGAP3 on immune infiltration and the immune microenvironment in gliomas was evaluated using immunofluorescence.Additionally,the cBioPortal database was used to analyze copy number variations and mutation sites of IQGAP3.Experimental validation was also performed to assess the effects of IQGAP3 on glioma cells and explore underlying mechanisms.Results:High IQGAP3 expression in gliomas is associated with an unfavorable prognosis,particularly in wild-type IDH and 1p/19q non-codeleted gliomas.Enrichment analysis revealed that IQGAP3 is involved in regulating the cell cycle,PI3K/AKT signaling,p53 signaling,and PLK1-related pathways.Furthermore,IQGAP3 expression may be closely related to the immunosuppressive microenvironment of glioblastoma.BRD-K88742110 and LY-303511 are potential drugs for targeting IQGAP3 in anti-glioma therapy.In vitro experiments showed that downregulation of IQGAP3 inhibits the proliferation and migration of glioma cells,with the PLK1/PI3K/AKT pathway potentially playing a crucial role in IQGAP3-mediated glioma progression.Conclusion:IQGAP3 shows promise as a valuable biomarker for diagnosis,prognosis,and immunotherapeutic strategies in gliomas.

Association of tumor budding with clinicopathological features and prognostic value in stage III-IV colorectal cancer

BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC.However,existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies.Consequently,this study investigated the correlation among TB categories,clinicopathological features,and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification.AIM To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC.METHODS The clinical data of 547 CRC patients were collected for this retrospective study.Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines.RESULTS Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy(P=0.004),clinical stage IV(P<0.001),≥4 regional lymph node metastases(P=0.004),left-sided colonic cancer(P=0.040),and Bd 2-3(P=0.002)were independent prognostic factors in patients with stage III-IV CRC.Moreover,the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3,both in the tumor stroma and its invasive margin.CONCLUSION TB has an independent predictive prognostic value in patients with stage III-IV CRC.It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.

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.

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.

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.

Identification of a novel inflammatory-related gene signature to evaluate the prognosis of gastric cancer patients

BACKGROUND Gastric cancer(GC)is a highly aggressive malignancy with a heterogeneous nature,which makes prognosis prediction and treatment determination difficult.Inflammation is now recognized as one of the hallmarks of cancer and plays an important role in the aetiology and continued growth of tumours.Inflammation also affects the prognosis of GC patients.Recent reports suggest that a number of inflammatory-related biomarkers are useful for predicting tumour prognosis.However,the importance of inflammatory-related biomarkers in predicting the prognosis of GC patients is still unclear.AIM To investigate inflammatory-related biomarkers in predicting the prognosis of GC patients.was constructed using the least absolute shrinkage and selection operator Cox regression model based on the GEO database.GC patients from the GSE26253 cohort were used for validation.Univariate and multivariate Cox analyses were used to determine the independent prognostic factors,and a prognostic nomogram was established.The calibration curve and the area under the curve based on receiver operating characteristic analysis were utilized to evaluate the predictive value of the nomogram.The decision curve analysis results were plotted to quantify and assess the clinical value of the nomogram.Gene set enrichment analysis was performed to explore the potential regulatory pathways involved.The relationship between tumour immune infiltration status and risk score was analysed via Tumour Immune Estimation Resource and CIBERSORT.Finally,we analysed the association between risk score and patient sensitivity to commonly used chemotherapy and targeted therapy agents.RESULTS A prognostic model consisting of three inflammatory-related genes(MRPS17,GUF1,and PDK4)was constructed.Independent prognostic analysis revealed that the risk score was a separate prognostic factor in GC patients.According to the risk score,GC patients were stratified into high-and low-risk groups,and patients in the high-risk group had significantly worse prognoses according to age,sex,TNM stage and Lauren type.Consensus clustering identified three subtypes of inflammation that could predict GC prognosis more accurately than traditional grading and staging.Finally,the study revealed that patients in the low-risk group were more sensitive to certain drugs than were those in the high-risk group,indicating a link between inflammation-related genes and drug sensitivity.CONCLUSION In conclusion,we established a novel three-gene prognostic signature that may be useful for predicting the prognosis and personalizing treatment decisions of GC patients.

Comprehensive analysis of the protein phosphatase 2A regulatory subunit B56ε in pan-cancer and its role and mechanism in hepatocellular carcinoma

BACKGROUND B56εis a regulatory subunit of the serine/threonine protein phosphatase 2A,which is abnormally expressed in tumors and regulates various tumor cell functions.At present,the application of B56εin pan-cancer lacks a comprehensive analysis,and its role and mechanism in hepatocellular carcinoma(HCC)are still unclear.The Cancer Genome Atlas,Genotype-Tissue Expression,Gene Expression Profiling Interactive Analysis,and Tumor Immune Estimation Resource databases were used to analyze B56εexpression,prognostic mutations,somatic copy number alterations,and tumor immune characteristics in 33 tumors.The relationships between B56εexpression levels and drug sensitivity,immuno-therapy,immune checkpoints,and human leukocyte antigen(HLA)-related genes were further analyzed.Gene Set Enrichment Analysis(GSEA)was performed to reveal the role of B56εin HCC.The Cell Counting Kit-8,plate cloning,wound healing,and transwell assays were conducted to assess the effects of B56εinterference on the malignant behavior of HCC cells.RESULTS In most tumors,B56εexpression was upregulated,and high B56εexpression was a risk factor for adrenocortical cancer,HCC,pancreatic adenocarcinoma,and pheochromocytoma and paraganglioma(all P<0.05).B56εexpression levels were correlated with a variety of immune cells,such as T helper 17 cells,B cells,and macro-phages.There was a positive correlation between B56εexpression levels with immune checkpoint genes and HLA-related genes(all P<0.05).The expression of B56εwas negatively correlated with the sensitivity of most chemotherapy drugs,but a small number showed a positive correlation(all P<0.05).GSEA analysis showed that B56εexpression was related to the cancer pathway,p53 downstream pathway,and interleukin-mediated signaling in HCC.Knockdown of B56εexpression in HCC cells inhibited the proliferation,migration,and invasion capacity of tumor cells.Core Tip:The expression of protein phosphatase 2A(PP2A)subunit B56εis up-regulated in most tumors,and its high expression is a risk factor for adrenocortical cancer,hepatocellular carcinoma(HCC),pancreatic adenocarcinoma,and pheochromocytoma and paraganglioma.B56εexpression levels correlate with immune cells,immune checkpoint genes,human leukocyte antigen-related genes,and the sensitivity of chemotherapy drugs.In HCC,B56εexpression is related to the cancer pathway.Knockdown of B56εexpression in HCC cells can inhibit the proliferation,migration and invasion capacity of tumor cells.Our study supports PP2A subunit B56εas a prognostic marker and potential therapeutic target for HCC.

Comprehensive analysis of clinical and biological value of ING family genes in liver cancer

BACKGROUND Liver cancer(LIHC)is a malignant tumor that occurs in the liver and has a high mortality in cancer.The ING family genes were identified as tumor suppressor genes.Dysregulated expression of these genes can lead to cell cycle arrest,senescence and/or apoptosis.ING family genes are promising targets for anticancer therapy.However,their role in LIHC is still not well understood.AIM To have a better understanding of the important roles of ING family members in LIHC.METHODS A series of bioinformatics approaches(including gene expression analysis,genetic alteration analysis,survival analysis,immune infiltration analysis,prediction of upstream microRNAs(miRNAs)and long noncoding RNAs(lncRNAs)of ING1,and ING1-related gene functional enrichment analysis)was applied to study the expression profile,clinical relationship,prognostic significance and immune infiltration of ING in LIHC.The relationship between ING family genes expression and tumor associated immune checkpoints was investigated in LIHC.The molecular mechanism of ING1 mediated hepatocarcinogenesis was preliminarily discussed.RESULTS mRNA/protein expression of different ING family genes in LIHC was analyzed in different databases,showing that ING family genes were highly expressed in LIHC.In 47 samples from 366 LIHC patients,the ING family genes were altered at a rate of 13%.By comprehensively analyzing the expression,clinical pathological parameters and prognostic value of ING family genes,ING1/5 was identified.ING1/5 was related to poor prognosis of LIHC,suggesting that they may play key roles in LIHC tumorigenesis and progression.One of the target miRNAs of ING1 was identified as hsa-miR-214-3p.Two upstream lncRNAs of hsa-miR-214-3p,U91328.1,and HCG17,were identified.At the same time,we found that the expression of ING family genes was correlated with immune cell infiltration and immune checkpoint genes.CONCLUSION This study lays a foundation for further research on the potential mechanism and clinical value of ING family genes in the treatment and prognosis of LIHC.

Action of circulating and infiltrating B cells in the immune microenvironment of colorectal cancer by single-cell sequencing analysis

BACKGROUND The complexity of the immune microenvironment has an impact on the treatment of colorectal cancer(CRC),one of the most prevalent malignancies worldwide.In this study,multi-omics and single-cell sequencing techniques were used to investigate the mechanism of action of circulating and infiltrating B cells in CRC.By revealing the heterogeneity and functional differences of B cells in cancer immunity,we aim to deepen our understanding of immune regulation and provide a scientific basis for the development of more effective cancer treatment strategies.AIM To explore the role of circulating and infiltrating B cell subsets in the immune microenvironment of CRC,explore the potential driving mechanism of B cell development,analyze the interaction between B cells and other immune cells in the immune microenvironment and the functions of communication molecules,and search for possible regulatory pathways to promote the anti-tumor effects of B cells.METHODS A total of 69 paracancer(normal),tumor and peripheral blood samples were collected from 23 patients with CRC from The Cancer Genome Atlas database(https://portal.gdc.cancer.gov/).After the immune cells were sorted by multicolor flow cytometry,the single cell transcriptome and B cell receptor group library were sequenced using the 10X Genomics platform,and the data were analyzed using bioinformatics tools such as Seurat.The differences in the number and function of B cell infiltration between tumor and normal tissue,the interaction between B cell subsets and T cells and myeloid cell subsets,and the transcription factor regulatory network of B cell subsets were explored and analyzed.RESULTS Compared with normal tissue,the infiltrating number of CD20+B cell subsets in tumor tissue increased significantly.Among them,germinal center B cells(GCB)played the most prominent role,with positive clone expansion and heavy chain mutation level increasing,and the trend of differentiation into memory B cells increased.However,the number of plasma cells in the tumor microenvironment decreased significantly,and the plasma cells secreting IgA antibodies decreased most obviously.In addition,compared with the immune microenvironment of normal tissues,GCB cells in tumor tissues became more closely connected with other immune cells such as T cells,and communication molecules that positively regulate immune function were significantly enriched.CONCLUSION The role of GCB in CRC tumor microenvironment is greatly enhanced,and its affinity to tumor antigen is enhanced by its significantly increased heavy chain mutation level.Meanwhile,GCB has enhanced its association with immune cells in the microenvironment,which plays a positive anti-tumor effect.

Low expression of fatty acid oxidation related gene ACADM indicates poor prognosis of renal clear cell carcinoma and is related to tumor immune infltration

This research aims to identify the key fatty acid beta-oxidation(FAO)genes that are altered in kidney renal clear cell carcinoma(KIRC)and to analyze the role of these genes in KIRC The Gene Expression Omnibus(GEO)and FAO datasets were used to identify these key genes.Wilcoxon rank sum test was used to assess the levels of acyl-CoA dehydrogenase medium chain(ACADM)between KIRC and non cancer samples.The logistic regression and Wilcoxon rank sum test were used to explore the association between ACADM and clinical features.The diagnostic performance of ACADM for KIRC was asessed using a diagnostic receiver operating ch aracteristic(ROC)curve.The co-expressed genes of ACADM were identifed in LinkedOmics database,and their function and pathway enrichment were analyzed.The correlation between ACADM expression level and immune infitration was analyzed by Gene Set Variation Analysis(GSVA)method Additionally,the proliferation,migration,and invasion abilities of KIRC cells were assessed after overexpressing ACADM.Following differential analysis and intersection,we identifed six hub genes,induding ACADM.We found that the expression level of ACADM was decreased in KIRC tissues and had a better diagnostic efect(AUC=0.916).Survival analysis suggested that patients with decreased ACADM expression had a worse prognosis.According to correlation analysis,a variety of dinical features were associated with the expression level of ACADML By analyzing the infiltration level of immune cells,we found that ACADM may be related to the enrichment of immune cells.Finally,ACADM overexpression inhibited proliferation,migration,and invasion of KIRC cells.In conclusion,our findings suggest that reduced ACADM expression in KIRC patients is indicative of poor prognosis.These results imply that ACADM may be a diagnostic and prognostic marker for individuals with KIRC,offering a reference for dinicians in diagnosis and treatment.

Identification of marker genes associated with N6-methyladenosine and autophagy in ulcerative colitis

BACKGROUND Both N6-methyladenosine(m6A)methylation and autophagy are considered relevant to the pathogenesis of ulcerative colitis(UC).However,a systematic exploration of the role of the com-bination of m6A methylation and autophagy in UC remains to be performed.AIM To elucidate the autophagy-related genes of m6A with a diagnostic value for UC.METHODS The correlation between m6A-related genes and autophagy-related genes(ARGs)was analyzed.Finally,gene set enrichment analysis(GSEA)was performed on the characteristic genes.Additionally,the expression levels of four characteristic genes were verified in dextran sulfate sodium(DSS)-induced colitis in mice.RESULTS GSEA indicated that BAG3,P4HB and TP53INP2 were involved in the inflammatory response and TNF-αsignalling via nuclear factor kappa-B.Furthermore,polymerase chain reaction results showed significantly higher mRNA levels of BAG3 and P4HB and lower mRNA levels of FMR1 and TP53INP2 in the DSS group compared to the control group.CONCLUSION This study identified four m6A-ARGs that predict the occurrence of UC,thus providing a scientific reference for further studies on the pathogenesis of UC.