Hepatic eosinophilic pseudotumor due to Fasciola hepatica infection mimicking intrahepatic cholangiocarcinoma: A case report

BACKGROUND Hepatic eosinophilic pseudotumor(HEPT)is a rare condition that mimics ma-lignant hepatic tumors,posing significant diagnostic challenges.This case report highlights the importance of considering parasitic infections like Fasciola hepatica(F.hepatica)in the differential diagnosis of hepatic masses,especially in endemic regions,to prevent unnecessary interventions.CASE SUMMARY A 40-year-old female presented with a 1-month history of epigastric pain and significant weight loss.Imaging revealed a hepatic mass,initially misdiagnosed as intrahepatic cholangiocarcinoma.Laboratory results showed marked eosinophilia,and histopathological examination confirmed significant eosinophilic infiltration without malignancy.Serological testing identified F.hepatica infection.The patient was treated with a single dose of triclabendazole,leading to complete symptom resolution and normalization of hepatic imaging findings within days.CONCLUSION HEPT due to F.hepatica can closely mimic malignancy;timely antiparasitic treat-ment is crucial for resolution.

Runoff simulation and hydropower resource prediction of the Kaidu River Basin in the Tianshan Mountains,China

The Tianshan Mountains of Central Asia,highly sensitive to climate change,has been comprehensively assessed for its ecosystem vulnerability across multiple aspects.However,studies on the region's main river systems and hydropower resources remain limited.Thus,examining the impact of climate change on the runoff and gross hydropower potential(GHP)of this region is essential for promoting sustainable development and effective management of water and hydropower resources.This study focused on the Kaidu River Basin that is situated above the Dashankou Hydropower Station on the southern slope of the Tianshan Mountains,China.By utilizing an ensemble of bias-corrected global climate models(GCMs)from Coupled Model Intercomparison Project Phase 6(CMIP6)and the Variable Infiltration Capacity(VIC)model coupled with a glacier module(VIC-Glacier),we examined the variations in future runoff and GHP during 2017-2070 under four shared socio-economic pathway(SSP)scenarios(SSP1-2.6,SSP2-4.5,SSP3-7.0,and SSP5-8.5)compared to the baseline period(1985-2016).The findings indicated that precipitation and temperature in the Kaidu River Basin exhibit a general upward trend under the four SSP scenarios,with the fastest rate of increase in precipitation under the SSP2-4.5 scenario and the most significant changes in mean,maximum,and minimum temperatures under the SSP5-8.5 scenario,compared to the baseline period(1980-2016).Future runoff in the basin is projected to decrease,with rates of decline under the SSP1-2.6,SSP2-4.5,SSP3-7.0,and SSP5-8.5 scenarios being 3.09,3.42,7.04,and 7.20 m^(3)/s per decade,respectively.The trends in GHP are consistent with runoff,with rates of decline in GHP under the SSP1-2.6,SSP2-4.5,SSP3-7.0,and SSP5-8.5 scenarios at 507.74,563.33,1158.44,and 1184.52 MW/10a,respectively.Compared to the baseline period(1985-2016),the rates of change in GHP under the SSP1-2.6,SSP2-4.5,SSP3-7.0,and SSP5-8.5 scenarios are-20.66%,-20.93%,-18.91%,and-17.49%,respectively.The Kaidu River Basin will face significant challenges in water and hydropower resources in the future,underscoring the need to adjust water resource management and hydropower planning within the basin.

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.

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.

Three-year field study on grass growth and soil hydrological properties in biochar-amended soil

Field monitoring was conducted to investigate and quantify the long-term effects of peanut shell biochar on soil-grass interaction over three years.Three 10 m5 m grassed plots were constructed in completely decomposed granitic soil.Two of them were amended,respectively,with 5%and 10%biochar contents(m^(3)/m^(3))for grass growth,while the third was without biochar amendment.During the threeyear monitoring,plant characteristics,saturated water permeability(k_(s))of grassed soil and soil suction were measured.The monitored results show that the grass leaf area index(LAI)and root length density(RLD)with biochar amendment were improved by 38%and 200%,respectively.In the grassed plot without biochar,a threshold RLD existed with a value of 1.7 cm/cm^(3),beyond which k_(s) raised pronouncedly.The threshold RLD increased by 52%when biochar content increased from 0%to 10%.This implies that biochar may restrict the increase in k_(s) of grassed soil due to the rise in the threshold RLD.The presence of biochar and grass can retain over 100%higher suction after heavy rainfalls,while 54%lower peak suction under evapotranspiration(ET)compared with the non-amended plot.Biochar can alleviate the negative effects on hydraulic properties caused by plant growth and reduce ET-induced excessive water loss.A 5%peanut shell biochar content is recommended for the long-term management of vegetated earthen infrastructures.

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.

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.

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.

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.

Identification and validation of a pyroptosis-related prognostic model for colorectal cancer based on bulk and single-cell RNA sequencing data

BACKGROUND Pyroptosis impacts the development of malignant tumors,yet its role in colorectal cancer(CRC)prognosis remains uncertain.AIM To assess the prognostic significance of pyroptosis-related genes and their association with CRC immune infiltration.METHODS Gene expression data were obtained from The Cancer Genome Atlas(TCGA)and single-cell RNA sequencing dataset GSE178341 from the Gene Expression Omnibus(GEO).Pyroptosis-related gene expression in cell clusters was analyzed,and enrichment analysis was conducted.A pyroptosis-related risk model was developed using the LASSO regression algorithm,with prediction accuracy assessed through K-M and receiver operating characteristic analyses.A nomo-gram predicting survival was created,and the correlation between the risk model and immune infiltration was analyzed using CIBERSORTx calculations.Finally,the differential expression of the 8 prognostic genes between CRC and normal samples was verified by analyzing TCGA-COADREAD data from the UCSC database.RESULTS An effective pyroptosis-related risk model was constructed using 8 genes-CHMP2B,SDHB,BST2,UBE2D2,GJA1,AIM2,PDCD6IP,and SEZ6L2(P<0.05).Seven of these genes exhibited differential expression between CRC and normal samples based on TCGA database analysis(P<0.05).Patients with higher risk scores demonstrated increased death risk and reduced overall survival(P<0.05).Significant differences in immune infiltration were observed between low-and high-risk groups,correlating with pyroptosis-related gene expression.CONCLUSION We developed a pyroptosis-related prognostic model for CRC,affirming its correlation with immune infiltration.This model may prove useful for CRC prognostic evaluation.

TREM-1 mediates interaction between substantia nigra microglia and peripheral neutrophils

Microglia-mediated neuroinflammation is considered a pathological feature of Parkinson's disease.Triggering receptor expressed on myeloid cell-1(TREM-1)can amplify the inherent immune response,and crucially,regulate inflammation.In this study,we found marked elevation of serum soluble TREM-1 in patients with Parkinson's disease that positively correlated with Parkinson's disease severity and dyskinesia.In a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease,we found that microglial TREM-1 expression also increased in the substantia nigra.Further,TREM-1 knockout alleviated dyskinesia in a mouse model of Parkinson's disease and reduced dopaminergic neuronal injury.Meanwhile,TREM-1 knockout attenuated the neuroinflammatory response,dopaminergic neuronal injury,and neutrophil migration.Next,we established an in vitro 1-methyl-4-phenyl-pyridine-induced BV2 microglia model of Parkinson's disease and treated the cells with the TREM-1 inhibitory peptide LP17.We found that LP17 treatment reduced apoptosis of dopaminergic neurons and neutrophil migration.Moreover,inhibition of neutrophil TREM-1 activation diminished dopaminergic neuronal apoptosis induced by lipopolysaccharide.TREM-1 can activate the downstream CARD9/NF-κB proinflammatory pathway via interaction with SYK.These findings suggest that TREM-1 may play a key role in mediating the damage to dopaminergic neurons in Parkinson's disease by regulating the interaction between microglia and peripheral neutrophils.

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.

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.

Modelling the water diversion of a sustainable cover system under humid climates

Extreme rainfall significantly threatens the safety of the landfill cover system,especially under humid climates.This study aims to provide design recommendations for a sustainable landfill cover system consisting of a low-permeability soil layer underlying a two-layer capillary barrier for humid climates.First,the numerical back-analysis was conducted for verification against a series of flume model tests.Then,a parametric study was performed to investigate the effects of inclination angle,particle size and layer thickness on the lateral diversion length(DL)of the three-layer cover system under the 100-year return period rainfall of humid climates.The results show that the water lateral DL of the cover system can be greatly enhanced by increasing the inclination angle from 3°to 18°.Moreover,the bottom layer of the cover system with a coarser d10 was more susceptible to the impact of the heavy rainfall,while this can be alleviated by increasing the thickness of the bottom layer.A dimensionless number,defined as the ratio of thickness and d_(10) of the bottom layer,is proposed for designing lateral diversion of the three-layer cover system under humid climates.To preserve the maximum DL,it is suggested that the proposed dimensionless number should be larger than 95 and 110 for the design of rainfall events with 50-year and 100-year return periods for humid climates,respectively.

GIS-based prediction method of shallow landslides induced by heavy rainfall in large mountainous areas

Rainwater runoff that does not infiltrate the soil during heavy rainfall may increase slope instability. The effect of runoff is usually neglected in conventional rainfall-induced slope failure analysis to simplify the model. To analyze the effect of runoff on slope stability, this study simultaneously simulated the effects of surface runoff and rainfall infiltration on bank slopes in the Three Gorges Reservoir Area. A shallow slope failure method that can be used to analyze runoff was proposed based on the modified Green-Ampt model, the simplified Saint-Venant model, and the infinite slope model. In this model, the modified Green–Ampt model was used to estimate the rainfall infiltration capacity and the wetting front depth. The eight-flow(D8) method and the simplified Saint-Venant model were selected to estimate the distribution of runoff. By considering the wetting front depth as the slip surface depth, the factor of safety of the slope could be determined using the infinite slope stability model. A comparison of the different models reveals that runoff can escalate the instability of certain slopes, causing stable slopes to become unstable. Comparison of the unstable areas obtained from the simulation with the actual landslide sites shows that the model proposed in this study can successfully predict landslides at these sites. The slope instability assessment model proposed in this study offers an alternative approach for estimating high-risk areas in large mountainous regions.

Microstructure and ablation behavior of Zr-based ultra-high-temperature gradient composites

To obtain high-performance Zr-based ultra-high-temperature composites,Zr-based ultra-high-temperature gradient composites were prepared by changing the laying method of the infiltrant via reactive melt infiltration.The effects of different infiltrant laying methods on the microstructure and ablative properties of Zr-based ultrahigh-temperature gradient composites were investigated.The results showed that the gradient structure of the Zr-based ultrahigh-temperature gradient composites differed when the composition ratio of the infiltrant was changed.When the thicknesses of the Zr/Mo/Si layers were 6/4/12 mm and 8/2/12 mm,the SiMoZrC solid solution content in the samples increased and decreased along the infiltration direction,respectively.The gradient samples were ablated in an oxyacetylene flame at 3000°C for 40 s.The ablation resistance of the sample was the highest when the infiltrant was a powder and the thickness of the Zr/Mo/Si layer was 6/4/12 mm.

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.

Effect of microalloying on wettability and interface characteristics of Zr-based bulk metallic glasses with W substrate

The infiltration casting method is widely employed for the preparation of ex-situ composite materials.However,the production of composite materials using this method must necessitates a comprehensive understanding of the wettability and interface characteristics between the reinforcing phase and the bulk metallic glasses(BMGs).This work optimized the composition of Zr-based BMGs through microalloying methods,resulting in a new set of Zr-based BMGs with excellent glass-forming ability.Wetting experiments between the Zr-based BMGs melts and W substrates were conducted using the traditional sessile drop method,and the interfaces were characterized utilizing a scanning electron microscope(SEM)equipped with energy dispersive X-ray spectroscopy(EDS).The work demonstrates that the microalloying method substantially enhances the wettability of the Zr-based BMGs melt.Additionally,the incorporation of Nb element impedes the formation of W-Zr phases,but the introduction of Nb element does not alter the extent of interdiffusion between the constituent elements of the amorphous matrix and W element,indicating that the influence of Nb element on the diffusion of individual elements is minute.

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.

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.