Unveiling the Power of Mitochondrial Fission and Fusion: A Five-Gene Signature for Personalized Prognosis in Gastric Cancer.

BACKGROUND: Mitochondrial fission and fusion play important roles in tumorigenesis, progression and therapy. Dysregulation of these processes may lead to tumor progression, and regulation of these processes may provide novel strategies for cancer therapy. The involvement of genes related to mitochondrial fission and fusion (MD) in gastric cancer (GC) remains poorly understood. OBJECTIVE: The aim of this study was to establish an MD gene signature for GC patients and to investigate its association with prognosis, tumor microenvironment and treatment response in GC. METHODS: We use the TCGA-GC database as the cohort, focusing specifically on genes associated with MD. We conducted identification and consistency clustering analysis of differentially expressed genes in MD, conducted MD gene mutation and copy number variation analysis, as well as correlation and functional enrichment analysis between MD gene cluster classification and immune infiltration. TCGA-GC and GSE15459 were used to construct training and validation cohorts for the model. We used various statistical methods, including Cox and Lasso regression, to develop the model. We validated the model using bulk transcriptome and single- cell transcriptome datasets (GSE13861, GSE26901, GSE66229, and GSE13450). We used GSEA enrichment, CIBERSORT algorithm, ESTIMATE, and TIDE to gain insight into the annotation of MD signature and the characterization of the tumor microenvironment. OncoPredict was used to analyze the relationship between the PRG signature and the drug sensitivity. We validated the expression of several key genes in MD signature on GC cell lines using quantitative real-time PCR (qRT-PCR). RESULTS: These MDs-related subtypes exhibited different prognosis and immune filtration patterns. A five-gene signature, comprising AGT, HCFC1, KIFC3, NOX4, and RIN1, was developed. There was a clear distinction in overall survival between low- and high-risk patients. The analyses showed further confirmation of the independent prognostic value of the gene signature. There was a notable correlation between the MD signature, immune infiltration and drug susceptibility. The expression levels of AGT, HCFC1, KIFC3, NOX4 and RIN1 mRNA were all increased in these GC cells. CONCLUSION: The MD signature has the capacity to significantly contribute to the prediction of personalized outcomes and the advancement of novel therapeutic strategies tailored for GC patients.

Expression Profile and Prognostic Values of IRX Family Members in Lung Adenocarcinoma.

BACKGROUND: The potential role of the iroquois homeobox (IRX) genes in tumorigenesis is a subject of interest, yet their specific involvement in lung adenocarcinoma (LUAD) has not been extensively examined. OBJECTIVE: This research endeavored to explore the impact of the IRX genes on the onset and progression of LUAD. METHODS: Utilizing data from The Cancer Genome Atlas (TCGA), samples of LUAD were selected for analysis. The influence of the IRX genes was scrutinized through various tools, including Kaplan-Meier Plotter, cBioPortal, and the R programming language (version 3.6.3), with gene expression levels being confirmed in cellular models via quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: It was observed that the levels of IRX1/2/3/6 were notably diminished in LUAD tissues when juxtaposed with healthy lung tissue. Conversely, the expression of IRX4 was found to be elevated in LUAD. Correlations were identified between IRX gene expression and several clinical parameters such as T stage, smoking history quantified in pack-years, lymph node involvement, patient gender, initial treatment responses, and smoking status. The diminished expression of IRX2/5 emerged as a significant indicator of an unfavorable prognosis in LUAD. The study also highlighted the potential of various IRX genes as diagnostic indicators for LUAD. These genes were implicated in the facilitation of LUAD's growth and spread through a range of biological pathways, encompassing the Ras signaling and more. Additionally, a pronounced link was discovered between the infiltration of immune cells and the expression patterns of the IRX genes. IRX genes were abnormally expressed in LUAD cell lines. CONCLUSION: IRX gene family could serve not only as indicators of LUAD prognosis but also as therapeutic targets for LUAD.

RPL22L1 is a novel biomarker for prognosis and immune infiltration in lung adenocarcinoma, promoting the growth and metastasis of LUAD cells by inhibiting the MDM2/P53 signaling pathway.

The ribosomal protein L22-like1 (RPL22L1) is a constituent of the 60 S ribosomal subunit whose function in lung adenocarcinoma (LUAD) remains ambiguous. This study aims to elucidate the role of RPL22L1 in LUAD through a thorough analysis and experimental validation. Our findings indicate that RPL22L1 exhibits abnormal expression patterns in various cancer types, including LUAD. Moreover, a statistically significant association was observed between elevated levels of RPL22L1 expression in LUAD patients and several clinical parameters, such as pathological stage (p = 0.0083) and gender (p = 0.0038). The high expression of RPL22L1 in LUAD demonstrated a significant association with poorer overall survival (OS) (p = 0.005), progression-free survival (PFS) (p = 0.027), and disease-specific survival (p = 0.015). The expression of RPL22L1 in LUAD (p = 0.005) was identified as an independent prognostic factor. Additionally, RPL22L1 expression in LUAD was found to be correlated with immune infiltration, immune checkpoint genes, TMB/MSI, and mRNAsi. Notably, the expression of RPL22L1 exhibited significant negative correlations with 1-BET-762, Trametinib, and WZ3105 in LUAD. The RPL22L1 gene exhibited up-regulation in multiple individual cells of LUAD, leading to a comparatively shorter PFS in the RPL22L1 variant group as opposed to the RPL22L1 variant-free group in LUAD. Significantly increased expression of RPL22L1 was noted in LUAD cell lines, where it was found to enhance the growth and metastasis of LUAD cells by suppressing the MDM2/P53 signaling pathway. Therefore, RPL22L1 may serve as a promising prognostic biomarker and therapeutic target for patients with LUAD.

G0 arrest gene patterns to predict the prognosis and drug sensitivity of patients with lung adenocarcinoma.

G0 arrest (G0A) is widely recognized as a crucial factor contributing to tumor relapse. The role of genes related to G0A in lung adenocarcinoma (LUAD) was unclear. This study aimed to develop a gene signature based on for LUAD patients and investigate its relationship with prognosis, tumor immune microenvironment, and therapeutic response in LUAD. We use the TCGA-LUAD database as the discovery cohort, focusing specifically on genes associated with the G0A pathway. We used various statistical methods, including Cox and lasso regression, to develop the model. We validated the model using bulk transcriptome and single-cell transcriptome datasets (GSE50081, GSE72094, GSE127465, GSE131907 and EMTAB6149). We used GSEA enrichment and the CIBERSORT algorithm to gain insight into the annotation of the signaling pathway and the characterization of the tumor microenvironment. We evaluated the response to immunotherapy, chemotherapy, and targeted therapy in these patients. The expression of six genes was validated in cell lines by quantitative real-time PCR (qRT-PCR). Our study successfully established a six-gene signature (CHCHD4, DUT, LARP1, PTTG1IP, RBM14, and WBP11) that demonstrated significant predictive power for overall survival in patients with LUAD. It demonstrated independent prognostic value in LUAD. To enhance clinical applicability, we developed a nomogram based on this gene signature, which showed high reliability in predicting patient outcomes. Furthermore, we observed a significant association between G0A-related risk and tumor microenvironment as well as drug susceptibility, highlighting the potential of the gene signature to guide personalized treatment strategies. The expression of six genes were significantly upregulated in the LUAD cell lines. This signature holds the potential to contribute to improved prognostic prediction and new personalized therapies specifically for LUAD patients.

Identification of Key Genes and Signaling Pathways in Entrectinibresistant Non-small Cell Lung Cancer Using Bioinformatic Analysis and Experimental Verification.

BACKGROUND: Entrectinib, a ROS1 inhibitor, is effective in patients with ROS1-positive non-small-cell lung cancer (NSCLC). However, entrectinib resistance remains a challenge worldwide. The biomarkers of entrectinib resistance and molecular mechanisms have not been clarified based on the Gene Expression Omnibus (GEO) database. OBJECTS: The aim of this study is to identify key genes and signaling pathways involved in the development of entrectinib-resistant NSCLC through bioinformatics analysis and experimental validation. METHODS: Differentially expressed genes (DEGs) were screened between entrectinib resistant and parental human NSCLC cell lines of the GSE214715 dataset, lung adenocarcinoma (LUAD) and non-tumor adjacent tissues of the GSE75037 dataset, and NSCLC and non-tumor adjacent tissues of the GSE18842 dataset. Functional enrichment analyses were performed, including Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Overlapped DEGs among those three datasets were identified using the Venn diagram package. The transcriptional levels of key genes were investigated using the University of ALabama at Birmingham CANcer data analysis Portal (UALCAN). The association between transcriptional levels of key genes and survival was analyzed using Kaplan-Meier Plotter (https://www.kmplot.com/analysis/). The correlations between hub genes and immune cell infiltration were investigated using the Tumor Immune Estimation Resource (TIMER) database. Specific signaling pathway enrichment analysis was performed using Gene Set Enrichment Analysis (GSEA) of LinkedOmics. Competitive endogenous RNA (ceRNA) networks, genome-wide association studies (GWAS), and drug sensitivity analyses of key genes were further investigated. The expression of ZEB2 was subsequently confirmed in both parental HCC78 cells and entrectinib-resistant HCC78 cells using real-time quantitative polymerase chain reaction (qRT-PCR). RESULTS: 708 DEGs were identified between entrectinib-resistant CUTO28 (CUTO28-ER) and parental CUTO28 cell lines in the GSE214715 dataset. One thousand three hundred and ninety-five DEGs were identified between entrectinib resistant (CUTO37-ER) and parental CUTO37 cell lines in the GSE214715 dataset. Eight hundred and forty-nine DEGs were identified between LUAD and non-tumor adjacent tissues in the GSE75037 dataset. Seven hundred and sevety-three DEGs were identified between NSCLC and non-tumor adjacent tissues in the GSE18842 dataset. Among these three datasets, seven overlapped DEGs were identified, including ZBED2, CHI3L2, CELF2, SEMA5A, ZEB2, S100A12, and PDK4. Among these seven overlapped DEGs, the expression levels of CHI3L2, ZEB2, and S100A12 were downregulated in those three datasets. The results of analysis using the UALCAN database showed that these three genes were significantly downregulated in LUAD and LUSC patients compared with the normal population. However, only the lower transcriptional level of ZEB2 was linked to worse survival in patients with lung cancer. GSEA analysis revealed that ZEB2 was significantly negatively correlated with nucleotide excision repair (NER) in LUAD, and homologous recombination (HR) and NER in LUSC, which were linked to drug resistance. A ceRNA network of THRB-AS1/ has-miR-1293/ ZEB2 in LUAD was established. CONCLUSION: We have identified core genes associated with non-small cell resistance to entrectinib, including CHI3L2, ZEB2, and S100A12. ZEB2 is a core gene associated with acquired resistance to entetinib in NSCLC.

Comprehensive Analysis and Experimental Validation of TLL2 as a Potential New Prognostic Biomarker Associated with Immune Infiltration in Lung Adenocarcinoma.

BACKGROUND: The precise function of Tolloid Like 2 (TLL2) remains uncertain within the context of Lung Adenocarcinoma (LUAD). OBJECTIVE: The primary objective of this investigation was to conduct a thorough analysis. METHODS: To assess its diagnostic utility, data from The Cancer Genome Atlas (TCGA) database were used to assess TLL2 expression in pan-cancer and LUAD. The study has also investigated the correlation between TLL2 expression levels and LUAD symptoms and prognosis. Furthermore, the study has explored possible regulatory networks involving TLL2, including its association with immune infiltration, tumor stemness index (mRNAsi), and drug sensitivity in LUAD. We have explored TLL2 expression in single-cell sequencing of LUAD and the genomic variation and clinical significance of TLL2 in LUAD. The expression of TLL2 has been validated in GSE87340 and cell lines by quantitative Real-time PCR (qRT-PCR). RESULTS: An abnormal expression of TLL2 has been found in pan-cancer and LUAD. In LUAD patients, elevated levels of TLL2 were significantly related to the T stage (p = 0.046) and the pathological stage (p = 0.016). The expression of TLL2 in patients with LUAD was significantly associated with poorer Overall Survival (OS) (p < 0.001). The expression of TLL2 was determined to be an independent predictor of poorer OS (p = 0.042). TLL2 was associated with ribosome, neuroactive ligand-receptor interaction, allograft rejection, ECM receptor interaction, asthma, porphyrin and chlorophyll metabolism, focal adhesion, pentose and glucuronate inter-conversions, and ascorbate and aldarate metabolism. The expression of TLL2 in LUAD was correlated with immune infiltration and mRNAsi. The expression of TLL2 was significantly and negatively correlated with TAK-715, XMD13-2, STF-62247, OSI-930, and EHT-1864 in LUAD. The TLL2 gene was up- -regulated in multiple individual LUAD cells. LUAD patients with altered TLL2 had a shorter PFS as opposed to those with unaltered TLL2. The expression of TLL2 was significantly increased in LUAD cells. CONCLUSION: For patients with LUAD, TLL2 may serve as an immunotherapeutic target and a useful prognosis biomarker.

Identification of Crucial Genes and Signaling Pathways in Alectinib-Resistant Lung Adenocarcinoma Using Bioinformatic Analysis.

Alectinib, a second-generation anaplastic lymphoma kinase (ALK) inhibitor, has been shown to be effective for patients with ALK-positive non-small cell lung cancer (NSCLC). However, alectinib resistance is a serious problem worldwide. To the best of our knowledge, little information is available on its molecular mechanisms using the Gene Expression Omnibus (GEO) database. In this study, the differentially expressed genes (DEGs) were selected from the gene expression profile GSE73167 between parental and alectinib-resistant human lung adenocarcinoma (LUAD) cell samples. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) annotation enrichment analyses were conducted using Database for Annotation, Visualization and Integrated Discovery (DAVID). The construction of protein-protein interaction (PPI) network was performed to visualize DEGs. The hub genes were extracted based on the analysis of the PPI network using plug-in cytoHubba of Cytoscape software. The functional roles of the key genes were investigated using Gene Expression Profiling Interactive Analysis (GEPIA), University of Alabama at Birmingham Cancer (UALCAN), Gene Set Enrichment Analysis (GSEA), and Tumor Immune Estimation Resource (TIMER) analysis. The networks of kinase, miRNA, and transcription-factor targets of SFTPD were explored using LinkedOmics. The drug sensitivity analysis of SFTPD was analyzed using the RNAactDrug database. Results showed a total of 144 DEGs were identified. Five hub genes were extracted, including mucin 5B (MUC5B), surfactant protein D (SFTPD), deleted in malignant brain tumors 1 (DMBT1), surfactant protein A2 (SFTPA2), and trefoil factor 3 (TFF3). The survival analysis using GEPIA displayed that low expression of SFTPD had a significantly negative effect on the prognosis of patients with LUAD. GSEA revealed that low expression of SFTPD was positively correlated with the pathways associated with drug resistance, such as DNA replication, cell cycle, drug metabolism, and DNA damage repair, including mismatch repair (MMR), base excision repair (BER), homologous recombination (HR), and nucleotide excision repair (NER). The SFTPD expression was negatively correlated with the drug sensitivity of alectinib according to RNAactDrug database. The expression of SFTPD was further validated in parental H3122 cells and alectinib-resistant H3122 cells by quantitative reverse transcription PCR (RT-qPCR). In conclusion, our study found that the five hub genes, especially low expression of SFTPD, are closely related to alectinib resistance in patients with LUAD.

Comprehensive analysis of ZNF692 as a potential biomarker associated with immune infiltration in a pan cancer analysis and validation in hepatocellular carcinoma.

Currently, the roles of ZNF692 have been documented exclusively in lung, colon, and cervical cancers. However, its involvement in pan cancer remains unknown. In this study, we employed bioinformatics analysis and experimental validation to investigate the role of ZNF692 in pan cancer. Our findings revealed aberrant expression of ZNF692 across various types of cancer. High expression of ZNF692 was associated with poor overall survival (OS) in ACC, COAD, KIRC, LAML, and LIHC. ZNF692 exhibited promising diagnostic potential in certain tumor types. A significant correlation was observed between high ZNF692 expression and advanced stages of ACC, BLCA, KICH, KIRC, LIHC, and OV. The expression of ZNF692 exhibited a significant association with microsatellite instability (MSI) in eight types of cancer and tumor mutational burden (TMB) in ten types of cancer. A noteworthy correlation was observed between ZNF692 expression and immune infiltration as well as immune checkpoints. Amplification of ZNF692 emerged as the most frequent alteration in pan cancer. ZNF692 was implicated in various biological processes, cellular components, and molecular functions within the context of pan cancer. It is plausible that ZNF692 may contribute to chemotherapy and potentially be linked to chemoresistance. We constructed a competing endogenous RNA (ceRNA) network involving AC009403.11/miR-126-3p/ZNF692 in hepatocellular carcinoma (HCC). The expression of ZNF692 exhibited a notable upregulation in HCC cell lines. Aberrant expression of ZNF692 was observed across various types of cancer. ZNF692 holds potential as a valuable diagnostic, prognostic, and therapeutic target in the context of pan cancer.

Perspectives on Thermochemical Recycling of End-of-Life Plastic Wastes to Alternative Fuels.

Due to its resistance to natural degradation and decomposition, plastic debris perseveres in the environment for centuries. As a lucrative material for packing industries and consumer products, plastics have become one of the major components of municipal solid waste today. The recycling of plastics is becoming difficult due to a lack of resource recovery facilities and a lack of efficient technologies to separate plastics from mixed solid waste streams. This has made oceans the hotspot for the dispersion and accumulation of plastic residues beyond landfills. This article reviews the sources, geographical occurrence, characteristics and recyclability of different types of plastic waste. This article presents a comprehensive summary of promising thermochemical technologies, such as pyrolysis, liquefaction and gasification, for the conversion of single-use plastic wastes to clean fuels. The operating principles, drivers and barriers for plastic-to-fuel technologies via pyrolysis (non-catalytic, catalytic, microwave and plasma), as well as liquefaction and gasification, are thoroughly discussed. Thermochemical co-processing of plastics with other organic waste biomass to produce high-quality fuel and energy products is also elaborated upon. Through this state-of-the-art review, it is suggested that, by investing in the research and development of thermochemical recycling technologies, one of the most pragmatic issues today, i.e., plastics waste management, can be sustainably addressed with a greater worldwide impact.

Comprehensive analysis of distal-less homeobox family gene expression in colon cancer.

BACKGROUND: The distal-less homeobox (DLX) gene family plays an important role in the development of several tumors. However, the expression pattern, prognostic and diagnostic value, possible regulatory mechanisms, and the relationship between DLX family genes and immune infiltration in colon cancer have not been systematically reported. AIM: We aimed to comprehensively analyze the biological role of the DLX gene family in the pathogenesis of colon cancer. METHODS: Colon cancer tissue and normal colon tissue samples were collected from the Cancer Genome Atlas and Gene Expression Omnibus databases. Wilcoxon rank sum test and t-test were used to assess DLX gene family expression between colon cancer tissue and unpaired normal colon tissue. cBioPortal was used to analyze DLX gene family variants. R software was used to analyze DLX gene expression in colon cancer and the relationship between DLX gene family expression and clinical features and correlation heat map. The survival package and Cox regression module were used to assess the prognostic value of the DLX gene family. The pROC package was used to analyze the diagnostic value of the DLX gene family. R software was used to analyze the possible regulatory mechanisms of DLX gene family members and related genes. The GSVA package was used to analyze the relationship between the DLX gene family and immune infiltration. The ggplot2, the survminer package, and the clusterProfiler package were used for visualization. RESULTS: DLX1/2/3/4/5 were significantly aberrantly expressed in colon cancer patients. The expression of DLX genes were associated with M stage, pathologic stage, primary therapy outcome, residual tumor, lymphatic invasion, T stage, N stage, age, perineural invasion, and history of colon polyps. DLX5 was independently correlated with the prognosis of colon cancer in multivariate analysis. DLX1/2/3/4/5/6 were involved in the development and progression of colon cancer by participating in immune infiltration and associated pathways, including the Hippo signaling pathway, the Wnt signaling pathway, several signaling pathways regulating the pluripotency of stem cells, and Staphylococcus aureus infection. CONCLUSION: The results of this study suggest a possible role for the DLX gene family as potential diagnostic or prognostic biomarkers and therapeutic targets in colon cancer.

Whole-genome sequencing identified novel mutations in a Chinese family with lynch syndrome.

Background: Lynch syndrome (LS) is caused by a germline mutation in one of the mismatch repair genes (MLH1, MSH2, MSH6, and PMS2) or in the EPCAM gene. The definition of Lynch syndrome is based on clinical, pathological, and genetic findings. Therefore, the identification of susceptibility genes is essential for accurate risk assessment and tailored screening programs in LS monitoring. Patients and methods: In this study, LS was diagnosed clinically in a Chinese family using Amsterdam II criteria. To further explore the molecular characteristics of this LS family, we performed whole genome sequencing (WGS) to 16 members in this family and summarized the unique mutational profiles within this family. We also used Sanger sequencing technology and immunohistochemistry (IHC) to verify some of the mutations identified in the WGS analysis. Results: We showed that mutations in mismatch repair (MMR) related genes, as well as pathways including DNA replication, base excision repair, nucleotide excision repair, and homologous recombination were enhanced in this family. Two specific variants, MSH2 (p.S860X) and FSHR (p.I265V) were identified in all five members with LS phenotypes in this family. The MSH2 (p.S860X) variant is the first reported variant in a Chinese LS family. This mutation would result in a truncated protein. Theoretically, these patients might benefit from PD-1 (Programmed death 1) immune checkpoint blockade therapy. The patients who received nivolumab in combination with docetaxel treatments are currently in good health. Conclusion: Our findings extend the mutation spectrum of genes associated with LS in MLH2 and FSHR, which is essential for future screening and genetic diagnosis of LS.

Upregulation of OTX2-AS1 is Associated With Immune Infiltration and Predicts Prognosis of Gastric Cancer.

BACKGROUND: It is unclear whether the long non-coding RNA (lncRNA) OTX2 antisense RNA 1 (OTX2-AS1) plays a pivotal role in gastric cancer (GC). An analysis of The Cancer Genome Atlas (TCGA) database data and bioinformatics was used to explore the relationship between OTX2-AS1 and GC in the current study. METHODS: We evaluated the relationship between clinical features and OTX2-AS1 expression, prognostic factors, and the significant involvement of OTX2-AS1 in function using various statistical methods, such as Kaplan-Meier method, Cox regression analysis, Gene Set Enrichment Analysis (GSEA), and immune infiltration analysis. GC cell lines were tested for OTX2-AS1 expression using qRT-PCR. RESULTS: A high level of OTX2-AS1 expression was significantly and negatively associated with Helicobacter pylori (H pylori) infection in GC patients (P = .006) and predicted a poorer overall survival (OS) (HR: 1.54; 95% CI: 1.10-2.14; P = .011), progression-free interval (PFI) (HR: 1.75; 95% CI: 1.22-2.51; P = .002) and disease-specific survival (DSS) (HR: 1.85; 95% CI: 1.21-2.85; P = .005) in GC patients. There was an independent correlation between OTX2-AS1 expression (HR: 1.771; 95% CI: 1.164-2.696; P = .008) and OS in patients with GC. There were differential enrichments for the OTX2-AS1 high expression phenotype in the olfactory transduction, G alpha (s) signaling events, keratinization, olfactory signaling pathway, and preimplantation embryo. OTX2-AS1 expression may be related to certain immune-infiltrating cells. Compared to gastric epithelial cells (GES-1), GC cell lines showed a significant increase in OTX2-AS1 expression. CONCLUSION: There was a significant association between OTX2-AS1 expression in GC patients and poor survival, suggesting that it may be a useful biomarker for prognosis and immunotherapy outcome of stomach adenocarcinoma (STAD) in GC.

Decreased Expression of a Novel lncRNA FAM181A-AS1 is Associated with Poor Prognosis and Immune Infiltration in Lung Adenocarcinoma.

Background: There is no clear information regarding the role of FAM181A antisense RNA 1 (FAM181A-AS1) in lung adenocarcinoma (LUAD). We explored the relationship between FAM181A-AS1 and LUAD using bioinformatics analysis and experimental validation in this study. Methods: Statistics and databases were used to evaluate the relationship between clinical features in LUAD patients and FAM181A-AS1 expression, prognostic factors, regulation network, and immune infiltration of FAM181A-AS1 in function. LUAD cell lines were tested for FAM181A-AS1 expression using qRT-PCR. Results: FAM181A-AS1 showed significantly low expression in LUAD patients. Low FAM181A-AS1 expression predicted a poorer overall survival (OS) (HR: 0.66; 95% CI: 0.49-0.88; P=0.005) and disease specific survival (DSS) (HR: 0.64; 95% CI: 0.44-0.92; P=0.017) of LUAD patients. There was also an independent correlation between low FAM181A-AS1 expression (HR: 0.547; 95% CI: 0.350-0.857; P=0.008) and OS in LUAD patients. The FAM181A-AS1 high-expression phenotype was differentially enriched for M phase, cellular senescence, cell cycle checkpoints, chromatin modifying enzymes, ESR-mediated signaling, DNA repair, G2/M checkpoints, HCMV infection, and DNA double-strand break repair. A correlation was found between the expression of FAM181A-AS1 and immune infiltrating cells. A significant decrease in FAM181A-AS1 expression was observed in LUAD cell lines compared to Beas-2B. Conclusion: There was a significant association between low FAM181A-AS1 expression in LUAD patients and poor survival and immune infiltration. The FAM181A-AS1 gene may provide a useful biomarker for LUAD prognosis and immunotherapy response.

Comprehensive Analysis of DMRT3 as a Potential Biomarker Associated with the Immune Infiltration in a Pan-Cancer Analysis and Validation in Lung Adenocarcinoma.

Doublesex and Mab-3 related Transcription Factor 3 (DMRT3) is associated with the prognosis of some tumors. It is possible to explore the role of DMRT3 in the cancer process using bioinformatic approaches and experimental validation. We comprehensively explored the clinical and immunological characteristics of DMRT3. The DMRT3 expression is abnormal in human cancers and correlates with clinical staging. A high DMRT3 expression is significantly associated with poor overall survival (OS) in KIRC, KIRP, LUAD, and UCEC. Amplification was the greatest frequency of the DMRT3 alterations in pan-cancer. The OS was significantly lower in the DMRT3 altered group than in the DMRT3 unaltered group (P = 0.0276). The DMRT3 expression was significantly associated with MSI in three cancer types and TMB in six cancer types. The DMRT3 expression was significantly correlated with the level of the immune cell infiltration and the immune checkpoint genes. The DMRT3 was involved in some pathways in pan-cancer. DMRT3 may play a role in chemotherapy and may be associated with chemoresistance. A ceRNA network of KCNQ1OT1/miR-335-5p/DMRT3 was constructed in LUAD. DMRT3 was significantly upregulated in the LUAD cell lines. DMRT3 was aberrantly expressed in pan-cancer and may promote tumorigenesis and progression via different mechanisms. DMRT3 can be used as a therapeutic target to treat cancer in humans.

Spatial Pattern Analysis of Xinjiang Tourism Resources Based on Electronic Map Points of Interest.

This study considers the Point of Interest data of tourism resources in Xinjiang and studies their spatial distribution by combining geospatial analysis methods, such as the average nearest neighbor index, standard deviation ellipse, kernel density analysis, and hotspot analysis, to explore their spatial distribution characteristics. Based on the analysis results, the following conclusions are made. Different categories of tourism resource sites have different spatial distributions, and all categories of tourism resources in Xinjiang are clustered in Urumqi city. The geological landscape resource sites are widely distributed and have a ring-shaped distribution in the desert area of southern Xinjiang. The biological landscape resources are distributed in a strip along the Tianshan Mountains. The water landscape resources are concentrated in the northern Xinjiang area. The site ruins are mostly distributed in the western region of Xinjiang. The distributions of the architectural landscape and entertainment and shopping resources are highly coupled with the distribution of cities. The distributions of the six categories of tourism resource points are in the northeast-southwest direction. The centripetal force and directional nature of the resource points of the water landscape are not obvious. The remaining five categories of resource points have their own characteristics. The distribution of resources in the site ruins is relatively even, and there are many hotspot areas in the geomantic and architectural landscapes, which are mainly concentrated in Bazhou and other places. The biological landscape has many cold-spot areas, distributed in areas such as Altai in northern Xinjiang and Hotan in southern Xinjiang. The remaining four categories have cold-spot and hotspot areas with different distributions. Tourism is an important thrust for economic development. The study of the distribution of tourism resources on the spatial distribution of tourism resources has clear guidance for later tourism development, can help the tourism industry optimize the layout of resources, and can promote tourism resources to achieve maximum benefits. The government can implement effective control and governance.

Lignin-based fluorescence-switchable graphene quantum dots for Fe3+ and ascorbic acid detection.

The synthesis of lignin-based graphene quantum dots (GQDs) with excellent fluorescence stability, quantum yield, and biocompatibility for sensitive and selective detection of Fe3+ and ascorbic acid (AA) has remained a challenging endeavor. Using an acidolysis process with 17.5% nitric acid followed by hydrothermal treatment at 200 °C, this study provided an improved synthesis route for the production of high-quality GQDs from alkali lignin. The nitrogen-doped GQDs exhibit remarkable fluorescence stability under a wide range of pH (3-10), duration (1-12 h), and [NaCl] (0-1000 mM) conditions, and have a high quantum yield of 28%. The GQDs or GQDs/Fe3+ sensing systems ([GQDs] at 50 mg L-1, [Fe3+] at 500 µmol L-1, and UV excitation at 370 nm) for fluorescence sensing of Fe3+ or AA have excellent sensitivity, selectivity, and reproducibility. For Fe3+ and AA, the limit of detection is 1.49 and 1.62 µmol L-1, respectively. Mechanism investigation shows that photoluminescence quenching is caused by the formation of GQDs-Fe3+ complexes, whereas fluorescence recovery is due to Fe3+ reduction by AA.

Low Expression of Long Noncoding RNA SLC26A4 Antisense RNA 1 Is an Independent Prognostic Biomarker and Correlate of Immune Infiltrates in Breast Cancer.

BACKGROUND Aberrant expression of long noncoding RNA (lncRNA) SLC26A4 antisense RNA 1 (SLC26A4-AS1) plays an important role in some cancer types. However, the clinical significance of SLC26A4-AS1 in patients with breast cancer (BC) and the possible regulatory mechanisms of SLC26A4-AS1 are unclear. MATERIAL AND METHODS Statistical analysis was used to assess the correlation between SLC26A4-AS1 expression and patients' clinical characteristics. The Kaplan-Meier method and Cox regression analysis were used to assess the correlation between SLC26A4-AS1 expression and prognosis. Gene set enrichment analysis (GSEA) and immuno-infiltration analysis were used to investigate the possible regulatory mechanisms of SLC26A4-AS1. RESULTS Low SLC26A4-AS1 expression in BC was associated with age (P<0.001), estrogen-receptor status (P<0.001), PAM50 (P<0.001), and menopause status (P<0.001). Low SLC26A4-AS1 expression predicted a poorer overall survival (OS) (hazard ratio [HR]: 0.56; 95% confidence interval [CI]: 0.40-0.78; P=0.001) and disease-specific survival (DSS) (HR: 0.57; 95% CI: 0.37-0.88; P=0.011). Also, SLC26A4-AS1 expression (HR: 0.298; 95% CI: 0.154-0.579; P<0.001) was independently correlated with OS in patients with BC. SLC26A4-AS1 was related to CYP2E1 reactions, protein export, mitochondrial_ciii_assembly, formation of adenosine triphosphate by chemiosmotic coupling, budding and maturation of HIV virion, cristae formation, biocarta proteasome pathway, endosomal sorting complex required for transport, and histone modification. SLC26A4-AS1 expression was associated with some types of immune infiltrating cells. CONCLUSIONS SLC26A4-AS1 expression was significantly associated with poor survival and immune infiltration in patients with BC. It may be a promising prognostic biomarker for BC.

LncRNA ADAMTS9-AS2 is a Prognostic Biomarker and Correlated with Immune Infiltrates in Lung Adenocarcinoma.

BACKGROUND: The role of long noncoding RNA (LncRNA) ADAMTS9 antisense RNA 2 (ADAMTS9-AS2) is unclear in lung adenocarcinoma (LUAD). The aim of this study was to explore the relationship between ADAMTS9-AS2 and LUAD, based on The Cancer Genome Atlas (TCGA) database and bioinformatics analysis. METHODS: Various statistical methods, Kaplan-Meier method, Cox regression analysis, GSEA, and immune infiltration analysis were used to evaluate the relationship between clinical features and ADAMTS9-AS2 expression, prognostic factors, and the significant involvement of ADAMTS9-AS2 in function. RESULTS: In LUAD patients, low expression of ADAMTS9-AS2 was associated with N stage (P=0.011), gender (P=0.002), number of packs smoked (P=0.024) and smoker (P<0.001). Low ADAMTS9-AS2 expression predicted a poorer overall survival (OS) (HR: 0.68; 95% CI: 0.51-0.91; P=0.01). And ADAMTS9-AS2 expression (HR: 0.626; 95% CI: 0.397-0.986; P=0.043) was independently correlated with OS in LUAD patients. Unwinding of DNA, extrinsic pathway, polo-like kinase-mediated events, cori cycle, MCM pathway, proteasome pathway, lagging strand synthesis and PCNA-dependent long patch base excision repair were differentially enriched in ADAMTS9-AS2 high expression phenotype. ADAMTS9-AS2 expression was correlated with certain immune infiltrating cells. CONCLUSION: In LUAD patients, ADAMTS9-AS2 expression was significantly associated with poor survival and immune infiltration. ADAMTS9-AS2 may be a promising biomarker of prognosis and response to immunotherapy for LUAD.

Whole-exome sequencing of rectal cancer identifies locally recurrent mutations in the Wnt pathway.

Locally recurrent rectal cancer (LRRC) leads to a poor prognosis and appears as a clinically predominant pattern of failure. In this research, whole-exome sequencing (WES) was performed on 21 samples from 8 patients to search for the molecular mechanisms of LRRC. The data was analyzed by bioinformatics. Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) were performed to validate the candidate genes. Immunohistochemistry was used to detect the protein expression of LEF1 and CyclinD1 in LRRC, primary rectal cancer (PRC), and non-recurrent rectal cancer (NRRC) specimens. The results showed that LRRC, PRC, and NRRC had 668, 794, and 190 specific genes, respectively. FGFR1 and MYC have copy number variants (CNVs) in PRC and LRRC, respectively. LRRC specific genes were mainly enriched in positive regulation of transcription from RNA polymerase II promoter, plasma membrane, and ATP binding. The specific signaling pathways of LRRC were Wnt signaling pathway, gap junction, and glucagon signaling pathway, etc. The transcriptional and translational expression levels of genes including NFATC1, PRICKLE1, SOX17, and WNT6 related to Wnt signaling pathway were higher in rectal cancer (READ) tissues than normal rectal tissues. The PRICKLE1 mutation (c.C875T) and WNT6 mutation (c.G629A) were predicted as "D (deleterious)". Expression levels of LEF1 and cytokinin D1 proteins: LRRC > PRC > NRRC > normal rectal tissue. Gene variants in the Wnt signaling pathway may be critical for the development of LRRC. The present study may provide a basis for the prediction of LRRC and the development of new therapeutic drugs.

Comprehensive Analysis of the Expression, Prognosis, and Biological Significance of OVOLs in Breast Cancer.

BACKGROUND: The study aimed to investigate the expression of OVOLs in breast cancer (BRCA) tissues and their value in prognosis. METHODS: ONCOMINE was used to analyze the expressions of OVOL1, OVOL2, and OVOL3 mRNA between BRCA tissues and normal breast tissues. The Wilcoxon rank sum test and t-test were used to assess the expression of OVOLs between BRCA tissues and unpaired/paired normal breast tissues. GEPIA and ROC curves were used to analyze the relationship between OVOLs expression and clinical pathological stage. Kaplan-Meier plotter was used to analyze prognosis. cBioPortal was used to analyze the mutation of OVOLs. GEPIA was used to analyze the co-expression of OVOLs. GO and KEGG analyses were performed by the DAVID software to predict the function of OVOLs co-expression genes. RESULTS: The expression of OVOL1/2 was significantly higher in BRCA tissues than in normal breast tissues. The OVOL3 expression correlated with tumor stage. The AUC of OVOLs was 0.757, 0.754, and 0.537, respectively. OVOL1 high expression was associated with shorter overall survival (HR: 1.48; 95% CI: 1.07-2.04; P=0.018). The OVOLs were associated with pathways including axon guidance, thyroid hormone signaling pathway, and ubiquinone and other terpenoid-quinone biosynthesis. CONCLUSION: OVOL1 is a new potential marker of prognosis in BRCA, and OVOL1/2 are potential therapeutic targets in BRCA.