Prediction of Tumor Microenvironment Characteristics and Treatment Response in Lung Squamous Cell Carcinoma by Pseudogene OR7E47P-related Immune Genes

Objective Pseudogenes are initially regarded as nonfunctional genomic sequences,but some pseudogenes regulate tumor initiation and progression by interacting with other genes to modulate their transcriptional activities.Olfactory receptor family 7 subfamily E member 47 pseudogene(OR7E47P)is expressed broadly in lung tissues and has been identified as a positive regulator in the tumor microenvironment(TME)of lung adenocarcinoma(LUAD).This study aimed to elucidate the correlation between OR7E47P and tumor immunity in lung squamous cell carcinoma(LUSC).Methods Clinical and molecular information from The Cancer Genome Atlas(TCGA)LUSC cohort was used to identify OR7E47P-related immune genes(ORIGs)by weighted gene correlation network analysis(WGCNA).Based on the ORIGs,2 OR7E47P clusters were identified using non-negative matrix factorization(NMF)clustering,and the stability of the clustering was tested by an extreme gradient boosting classifier(XGBoost).LASSO-Cox and stepwise regressions were applied to further select prognostic ORIGs and to construct a predictive model(ORPScore)for immunotherapy.The Botling cohorts and 8 immunotherapy cohorts(the Samstein,Braun,Jung,Gide,IMvigor210,Lauss,Van Allen,and Cho cohorts)were included as independent validation cohorts.Results OR7E47P expression was positively correlated with immune cell infiltration and enrichment of immune-related pathways in LUSC.A total of 57 ORIGs were identified to classify the patients into 2 OR7E47P clusters(Cluster 1 and Cluster 2)with distinct immune,mutation,and stromal programs.Compared to Cluster 1,Cluster 2 had more infiltration by immune and stromal cells,lower mutation rates of driver genes,and higher expression of immune-related proteins.The clustering performed well in the internal and 5 external validation cohorts.Based on the 7 ORIGs(HOPX,STX2,WFS,DUSP22,SLFN13,GGCT,and CCSER2),the ORPScore was constructed to predict the prognosis and the treatment response.In addition,the ORPScore was a better prognostic factor and correlated positively with the immunotherapeutic response in cancer patients.The area under the curve values ranged from 0.584 to 0.805 in the 6 independent immunotherapy cohorts.Conclusion Our study suggests a significant correlation between OR7E47P and TME modulation in LUSC.ORIGs can be applied to molecularly stratify patients,and the ORPScore may serve as a biomarker for clinical decision-making regarding individualized prognostication and immunotherapy.

Advancement and Applications of Nanotherapy for Cancer Immune Microenvironment

Cancer treatment has evolved rapidly due to major advances in tumor immunity research.However,due to the complexity,heterogeneity,and immunosuppressive microenvir-onment of tumors,the overall efficacy of immunotherapy is only 20%.In recent years,nanoparticles have attracted more attention in the field of cancer immunotherapy because of their remarkable advantages in biocompatibility,precise targeting,and controlled drug delivery.However,the clinical application of nanomedicine also faces many problems concerning biological safety,and the synergistic mechanism of nano-drugs with immunity remains to be elucidated.Our study summarizes the functional characteristics and regulatory mechanisms of nanoparticles in the cancer immune microenvironment and how nanoparticles activate and long-term stimulate innate immunity and adaptive immunity.Finally,the current problems and future development trends regarding the application of nanoparticles are fully discussed and prospected to promote the transformation and application of nanomedicine used in cancer treatment.

HUMAN DRIVING MECHANISM OF REGIONAL LAND USE CHANGE:A CASE STUDY OF KARST MOUNTAIN AREAS OF SOUTHWESTERN CHINA

Based on analysis of the change of land use and related social- economic factors in karst mountain areas of southwestern China, the index system characterizing land use change and its human driving forces in county scale is put forward. Then the relationship of land use change and the driving forces is studied by statistic analysis to identify quantitatively the contribution of human forces and their differences in driving land use change. Moreover, taking the Luodian County as the case, a model simulating the annual change of cultivated land area under the driving of human forces is built. Result of the study will supply reference for the management of the relationship of man and land in karst mountain areas of southern- western China, and accumulate research experience for further study on land use/cover change.

Effect of depressurizing speed on mold filling behavior and entrainment of oxide film in vacuum suction casting of A356 alloy

The effect of depressurizing speed on mold filling behavior and entrainment of oxide film of A356 alloy was studied. Themold filling behavior and velocity fields were recorded by water simulation with particle image velocimetry. The results show thatthe gate velocity first increased dramatically, then changed with the depressurizing speed: the gate velocity increased slowly atrelatively high depressurizing speed; at reasonable depressurizing speed, the gate velocity kept unchanged; while at lowerdepressurizing speed, the gate velocity decreased firstly and then kept unchanged. High gate velocity results in melt falling backunder gravity at higher speed. The falling velocity is the main factor of oxide film entrainment in vacuum suction casting. The designcriterion of depressurizing rate was deduced, and the A356 alloy castings were poured to test the formula. The four-point bend testand Weibull probability plots were applied to assessing the fracture mechanisms of the as-cast A356 alloy. The results illuminate amethod on designing suitable depressurizing speed for mold filling in vacuum suction casting.

Analysis of imbibition of n-alkanes in kerogen slits by molecular dynamics simulation for characterization of shale oil rocks

Shale oil formations contain both inorganic and organic media.The organic matter holds both free oil in the pores and dissolved oil within the kerogen molecules.The free oil flow in organic pores and the dissolved oil diffusion in kerogen molecules are coupled together.The molecular flow of free n-alkanes is an important process of shale oil accumulation and production.To study the dynamics of imbibition process of n-alkane molecules into kerogen slits,molecular dynamics(MD)simulations are conducted.Effects of slit width,temperature,and n-alkane types on the penetration speed,dynamic contact angle,and molecular conformations were analyzed.Results showed that molecular transportation of n-alkanes is dominated by molecular structure and molecular motion at this scale.The space-confinement conformational changes of molecules slow down the filling speeds in the narrow slits.The n-alkane molecules with long carbon chains require more time to undergo conformational changes.The high content of short-chain alkanes and high temperature facilitate the flow of alkane mixtures in kerogen slits.Results obtained from this study are useful for understanding the underlying nanoscale flow mechanism in shale formations.

Arsenic contamination caused by roxarsone transformation with spatiotemporal variation of microbial community structure in a column experiment

Arsenic contamination from roxarsone in livestock manure is common,and livestock manure continuously accumulates in the open environment.Evaluations of the environmental processes of As mobilization and transformation are critical for predicting the fate of As compounds after roxarsone degradation.In this study,spatiotemporal variations in As species and microbial community structure were characterized using laboratory column experiments with background soil collected from Yanggu County(northern Shandong Plain,China),a region of intense poultry production.Organic and inorganic arsenic were detected by high-performance liquid chromatography(HPLC)and HPLC with hydride generation atomic fluorescence spectrometry(HPLC-HG-AFS),respectively.High-throughput sequencing technology was used to describe microbial diversity.Results showed that roxarsone was transformed completely within 7 days,and A_(s)(Ⅲ)and As(Ⅴ)were the major degradation products.The concentration of A_(s)(Ⅲ)was much lower than that of As(Ⅴ).The A_(s)(Ⅲ)concentration increased significantly after Day 14,whereas the A_(s)(Ⅴ)concentration increased significantly after Day 84,indicating that A_(s)(Ⅲ)was initially produced.The microbial community structure changed significantly as roxarsone transformed into various As compounds.A critical and dominant bacterial strain,norank_f__Family_XVⅢ,was found to be related to the degradation of roxarsone into As(Ⅲ).This study improves our understanding of the fate of As species released from poultry litter to soil and groundwater,which is a threat to human health and environment.

Microstructure and elevated-temperature tensile properties of differential pressure sand cast Mg-4Y-3Nd-0.5Zr alloy

The microstructures of an Mg-4Y-3Nd-0.5Zr alloy by differential pressure casting were investigated using scanning electron microscopy （SEM） and transmission electron microscopy （TEM）, and its tensile deformation behavior was measured using a Gleeble1500D themo-simulation machine in the temperature range of 200 to 400 ℃ at initial strain rates of 5×10^-4 to 10^-1 s^-1. Results show that the as-cast microstructure consists of primary α-Mg phase and bone-shaped Mg5RE eutectic phase distributed along the grain boundary. The eutectic phase is dissolved into the matrix after solution treatment and subsequently precipitates during peak aging. Tensile deformation tests show that the strain rate has little effect on stress under 300 ℃. Tensile stress decreases with an increase in temperature and the higher strain rate leads to an increase in stress above 300 ℃. The fracture mechanism exhibits a mixed quasi-cleavage fracture at 200 ℃, while the fracture above 300 ℃ is a ductile fracture. The dimples are melted at 400 ℃ with the lowest strain rate of 10^-4 s^-1.

Impacts of zinc layer and pouring method on interface performance for Al-22Si/ZL104 bi-metal

Bi-metal material consisting of spray-formed Al-22Si and ZL104 is a suitable candidate for applications in internal combustion engines. This research investigated the effects of surface treatment and appropriate gating system on the microstructures and mechanical properties in evaluating the optimal strategy for producing high quality bi-metal materials. The bi-metal materials were prepared using ZL104 gravity casting by different pouring types around the spray-formed AI-22Si with varied surface treatments. The wettability between AI-22Si and ZL104 was significantly improved when Zn coating was used to remove the natural oxide layer. This research also obtained the improved interfacial microstructures and interracial bonding strength for materials when applying the appropriate pouring method. The hardness profiles of AI-22Si/ZL104 bi-metal were consistent with the observed microstructures. The average tensile strength of the bi-metal material with zinc coating is -42.3 MPa, which is much higher than that with oxide film at -10 MPa. The process presented is a promising and effective approach for developing materials in the automotive industry.

Homogenization heat treatment for an additively manufactured precipitation-hardening high-entropy alloy

A precipitation-hardening high-entropy alloy(HEA),(FeCoNi)_(86)Al_(7) Ti_(7),was successfully fabricated using selective laser melting(SLM).Severe segregation of Ti occurred at the boundaries of dislocation cells.Therefore,homogenization heat treatment at 1150℃for 0.5 h was performed to alleviate the microsegregation.After homogenization,almost no dislocation cells were left in the grains,and recrystallization occurred as the average grain size increased from 37 to 54μm.Compared with the initial as-built HEA,the ductility of the HEA increases significantly from 29%to 40%,and the strength decreases slightly from 710 to 606 MPa.For further aging,pre-homogenization can decrease the precipitation of ordered L2_(1) phases.Because void has a high propensity to initiate from the matrix/L2_(1) incoherent interface,pre-homogenization reduced the number of weak points,thus considerably improving the plastic deformation ability of the aged HEA by 36%.In addition,the strengthening mechanism has also been analyzed for the aged HEA.It was revealed that the coherent L1_(2)precipitate contributed the most to the increased strength.

Effect of Double Oxide Film Defects on Mechanical Properties of As-Cast C95800 Alloy

The morphology of double oxide film defects and their influence on the tensile mechanical properties of a commercial Cu-Al （C95800） alloy were investigated in this study. Plane castings were produced with two types of pouting systems, and their tensile properties were measured and then analyzed by means of Weibull statistics method. The fracture surfaces of the tensile specimens were examined using scanning electron microscopy equipped with energy-dispersive spectroscopy. A large amount of double oxide film defects were observed on the tensile fractured specimens of the topfilled plane castings, and their chemical composition is identified to be Al2O3. Weibull statistics analyses showed that the double oxide film defects significantly reduce mechanical properties of the castings investigated. Furthermore, the ultimate tensile strength is more obviously deteriorated by double oxide film defects than elongation.