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.

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.

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.

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.

Identification of Core Prognosis-Related Candidate Genes in Chinese Gastric Cancer Population Based on Integrated Bioinformatics.

BACKGROUND: Gastric cancer (GC) is one of the leading causes of cancer-related mortality worldwide. There are great geographical differences in the incidence of GC, and somatic mutation rates of driver genes are also different. The present study is aimed at screening core prognosis-related candidate genes in Chinese gastric cancer population based on integrated bioinformatics for the early diagnosis and prognosis of GC. METHODS: In the present study, the differentially expressed genes (DEGs) in GC were identified using four microarray datasets from the Gene Expression Omnibus (GEO) database. The samples of these datasets were all from China. Functional enrichment analysis of DEGs was conducted to evaluate the underlying molecular mechanisms involved in GC. Protein-protein interaction (PPI) network and cytoHubba were performed to determine hub genes associated with GC. Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) were performed to validate the hub genes. RESULTS: A total of 240 DEGs were obtained through the RRA method, including 80 upregulated genes and 160 downregulated genes. Upregulated genes were mainly enriched in extracellular matrix organization, extracellular matrix, and extracellular matrix structural constituent. The downregulated genes were mainly enriched in digestion, extracellular space, and oxidoreductase activity. The KEGG pathway enrichment analysis showed that the upregulated genes were mainly associated with ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling pathway. And downregulated genes were mainly associated with the metabolism of xenobiotics by cytochrome P450, metabolic pathways, and gastric acid secretion. The transcriptional and translational expression levels of the genes including COL1A1, COL5A2, COL12A1, and VCAN were higher in GC tissues than normal tissues. CONCLUSION: A total of four genes including COL1A1, COL5A2, COL12A1, and VCAN were considered potential GC biomarkers in the Chinese population. And ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling pathway were revealed to be important mechanisms of GC. Our findings provide novel insights into the occurrence and progression of GC in the Chinese population.

Genotoxic effects and proteomic analysis on Allium cepa var. agrogarum L. root cells under Pb stress.

Ionic lead (Pb) in the environment has accumulated due to anthropogenic activities, causing a potential threat to plants and plant consumers. We conducted this study to reveal the molecular mechanism of Pb stress response in plants. The effects of Pb (5.0 and 15.0 µM) on mitosis, DNA replication, gene expression and proteins in root-tip cells of Allium cepa var. agrogarum L. were addressed. The results indicated that root growth was inhibited dramatically in Pb treatment groups. Chromosomal aberrations were observed and the mitotic index decreased during Pb treatments at different concentrations. The accumulation of reactive oxygen species (ROS) in onion roots was induced by Pb stress. Pb increased DNA damage and suppressed cell cycle progression. The above toxic effects got more serious with increasing Pb concentration and prolonging exposure time. A total of 17 proteins were expressed differentially between control and Pb exposure groups. Under Pb treatment, the decreased expression of Anx D1 indicated decreased defensive response; the decreased expression of SHMT1 indicated decreased respiration; the decreased expression of COMT2 indicated decreased response of other funtions; the increased expression of NDPK indicated increased transcription and protein synthesis; the increased expression of PR1 and CHI1 indicated increased pathogen invasion; the increased expression of ORC5 and MPK5 indicated the reduced DNA replicating activity; the decreased expression of POLD1 indicated the reduced DNA repair activity. Our results provide new insights at the proteomic level into the Pb-induced responses, defensive responses and toxic effects, and provide new molecular markers of the early events of plant responses to Pb toxicity.

Bioinformatics analysis of BBX family genes and its response to UV-B in Arabidopsis thaliana.

The B-box proteins (BBXs) are a family of zinc finger proteins containing one/two B-box domain(s), which play important roles in plant growth and development. Though the Arabidopsis thaliana BBX family genes have been identified and named, no systematic study has taken on BBX family genes involved in the regulation of UV-B induced photomorphogenesis in Arabidopsis thaliana. In our previous report, BBX24/STO was demonstrated to be a negative regulator in UV-B signaling pathway in Arabidopsis. In the present study, the total 32 BBX family genes from Arabidopsis were analyzed, including their structures, conserved domains, phylogenetic relationships, promoter cis-regulatory elements, expression patterns under UV-B radiation. The expression profile of GEO Datasets (GSE117199) related to UV-B in NCBI database was analyzed. qRT-PCR was used to validate the expression profile of several BBX genes in Arabidopsis treated with UV-B. The promoters of AtBBXs contained cis-acting elements that respond to light and hormones, including ethylene, auxin (IAA), abscisic acid (ABA), gibberellin (GA) and methyl jasmonate (MeJA). BBX24 and BBX25 were collinear blocks, suggesting that BBX25 may also be involved in UV-B signal transduction. Expression profile analysis and qRT-PCR validation showed that UV-B induced up-regulation of BBX1, BBX7, BBX20, BBX25 and BBX32, suggesting that AtBBXs were mainly involved in UV-B photomorphogenesis. It is predicted that BBX1, BBX7, BBX20 and BBX25 may be new members in response to UV-B signaling.

Formaldehyde and VOC emissions from plywood panels bonded with bio-oil phenolic resins.

Pyrolysis bio-oil was used to partially substitute for phenol in reacting with formaldehyde for the production of bio-oil phenol formaldehyde plywood (BPFP) panels, with the phenol substitution ratio being 20%, 40%, or 60%. Emissions of formaldehyde and volatile organic compounds (VOCs) from the BPFP panels were studied using solid-phase micro-extraction (SPME) followed by headspace gas chromatography/mass spectrometry (GC/MS), and were compared to those from the phenol formaldehyde plywood (PFP) panels. The sources for VOCs were analyzed, and the health risks associated with the BPFP were examined. Results showed that at 80 °C: (1) Formaldehyde emissions from the BPFP panels were increased to about 4 times that of PFP; (2) VOCs emissions were significantly reduced by up to 84.9% mainly due to the greatly reduced phenol emissions, although the total number of VOCs was increased from 20 to 35; (3) BPFP presents greatly increased carcinogenic and non-carcinogenic health risks because of its much stronger emissions of formaldehyde, N,N-dimethylformamide, benzofuran, furfural, and many chemicals from the bio-oil. It is highly advisable that the health risks are properly taken care of before the wide application of BPFP, or similar bio-oil based engineered wood products.

Quantitative Proteomic Analyses Identify STO/BBX24 -Related Proteins Induced by UV-B.

Plants use solar radiation for photosynthesis and are inevitably exposed to UV-B. To adapt to UV-B radiation, plants have evolved a sophisticated strategy, but the mechanism is not well understood. We have previously reported that STO (salt tolerance)/BBX24 is a negative regulator of UV-B-induced photomorphogenesis. However, there is limited knowledge of the regulatory network of STO in UV-B signaling. Here, we report the identification of proteins differentially expressed in the wild type (WT) and sto mutant after UV-B radiation by iTRAQ (isobaric tags for relative and absolute quantitation)-based proteomic analysis to explore differential proteins that depend on STO and UV-B signaling. A total of 8212 proteins were successfully identified, 221 of them were STO-dependent proteins in UV-B irradiated plants. The abundances of STO-dependent PSB and LHC (light-harvesting complex) proteins in sto mutants decreased under UV-B radiation, suggesting that STO is necessary to maintain the normal accumulation of photosynthetic system complex under UV-B radiation to facilitate photosynthesis photon capture. The abundance of phenylalanine lyase-1 (PAL1), chalcone synthetase (CHS), and flavonoid synthetase (FLS) increased significantly after UV-B irradiation, suggesting that the accumulation of flavonoids do not require STO, but UV-B is needed. Under UV-B radiation, STO stabilizes the structure of antenna protein complex by maintaining the accumulation of PSBs and LHCs, thereby enhancing the non-photochemical quenching (NPQ) ability, releasing extra energy, protecting photosynthesis, and ultimately promoting the elongation of hypocotyl. The accumulation of flavonoid synthesis key proteins is independent of STO under UV-B radiation. Overall, our results provide a comprehensive regulatory network of STO in UV-B signaling.

STO and GA negatively regulate UV-B-induced Arabidopsis root growth inhibition.

Studies on UV-B-induced plant photomorphogenesis mainly focus on Arabidopsis shoots (hypocotyl, leaf, petiole, and stem) but less on roots. In the present research, the low-level UV-B (0.2 W·m-2) induced a decrease in the number of root cells in the meristem zone and an inhibition of the cell length in the maturation zone of roots in Arabidopsis thaliana L.Heynh (Col-0). UV-B-induced root growth inhibition was recovered by the addition of GA3 to culture media. GA3 played an important role in UV-B-induced inhibition of root growth. The cop1-4 mutant with more meristem cell and longer mature cells exhibited longer root length under low-level UV-B. COP1 acted as a positive regulator of root growth under UV-B, through regulation of cell division and elongation. The sto mutant exhibited a shorter root length under UV-B with similar cell length but fewer meristem cells compared with wild type (Col-0). STO only regulated cell division, but cell expansion was not affected. UV-B radiation also inhibited the root growth of uvr8 mutant, and the degree of inhibition was greater than for wild type (Ler). UV-B inhibited the growth of Arabidopsis root, possibly because it changes the GA signal and inhibited cell division and cell elongation, which be related to COP1 and STO genes.