Identification of key genes for atherosclerosis in different arterial beds.

Atherosclerosis (AS) is the pathologic basis of various cardiovascular and cerebrovascular events, with a high degree of heterogeneity among different arterial beds. However, mechanistic differences between arterial beds remain unexplored. The aim of this study was to explore key genes and potential mechanistic differences between AS in different arterial beds through bioinformatics analysis. Carotid atherosclerosis (CAS), femoral atherosclerosis (FAS), infrapopliteal atherosclerosis (IPAS), abdominal aortic atherosclerosis (AAS), and AS-specific differentially expressed genes (DEGs) were screened from the GSE100927 and GSE57691 datasets. Immune infiltration analysis was used to identify AS immune cell infiltration differences. Unsupervised cluster analysis of AS samples from different regions based on macrophage polarization gene expression profiles. Weighted gene co-expression network analysis (WGCNA) was performed to identify the most relevant module genes with AS. Hub genes were then screened by LASSO regression, SVM-REF, and single-gene differential analysis, and a nomogram was constructed to predict the risk of AS development. The results showed that differential expression analysis identified 5, 4, 121, and 62 CAS, FAS, IPAS, AAS-specific DEGs, and 42 AS-common DEGs, respectively. Immune infiltration analysis demonstrated that the degree of macrophage and mast cell enrichment differed significantly in different regions of AS. The CAS, FAS, IPAS, and AAS could be distinguished into two different biologically functional and stable molecular clusters based on macrophage polarization gene expression profiles, especially for cardiomyopathy and glycolipid metabolic processes. Hub genes for 6 AS (ADAP2, CSF3R, FABP5, ITGAX, MYOC, and SPP1), 4 IPAS (CLECL1, DIO2, F2RL2, and GUCY1A2), and 3 AAS (RPL21, RPL26, and RPL10A) were obtained based on module gene, gender stratification, machine learning algorithms, and single-gene difference analysis, respectively, and these genes were effective in differentiating between different regions of AS. This study demonstrates that there are similarities and heterogeneities in the pathogenesis of AS between different arterial beds.

Projecting the response of ecological risk to land use/land cover change in ecologically fragile regions.

Anthropogenic activities have dramatically altered land use/land cover (LULC), leading to ecosystem service (ES) degradation and further ecological risks. Ecological risks are particularly serious in ecologically fragile regions because trade-offs between economic development and ecological protection are prominent. Thus, ways in which to assess the response of ecological risks to LULC change under each development scenario in ecologically fragile regions remain challenging. In this study, future LUCC and its impact on ESs under four development scenarios in 2040 in western Jilin Province were predicted using a patch-generating land use simulation model and the Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) model. Ecological risk was assessed based on future LUCC possibilities, and potential ES degradation and potential drivers of ecological risks were explored using a geographic detector. The results showed that the cropland development scenario (CDS) would experience large-scale urbanization and cropland expansion. Carbon storage (CS), habitat quality (HQ), and water purification (WP) degraded the most under the CDS, and grain yield (GY) and water yield (WY) degraded the most under the ecological protection scenario (EPS). The LUCC probability under the CDS (14.37 %) was the highest, while the LUCC probability under the comprehensive development scenario (CPDS) (8.68 %) was the lowest. The risk of WP degradation was greatest under the CDS, but the risk of soil retention (SR) degradation was greatest under the natural development scenario (NDS), EPS, and CPDS. Ecological risk coverage was the largest (98.04 %), and ecological risks were the highest (0.21) under the CDS, while those under the EPS were the opposite. Distance to roads and population density had a higher impact on ecological risks than other drivers. Further attention should be given to the ecological networks and pattern establishment in urbanized regions. This study will contribute to risk prevention and sustainable urban and agricultural development.

An enhanced model for environmental dry eye: Exploring pathological features and underlying factors.

This study aimed to develop an enhanced environmental dry eye (EDE) model that accurately reproduces the etiology of prolonged visual fatigue and investigates the underlying pathological features. A total of 40 adult SPF-grade Wistar rats were randomly assigned to control (n = 20) and model (n = 20) groups. Rats in the control group were maintained under normal conditions, while rats in the model group were exposed to a controlled frontal airflow of 2-4 m/s from a fan for 7.5 h daily while placed on a suspended cylindrical wire mesh frame. Various assessments were performed at different time points during the 14-day experiment, including blink frequency, tear secretion (phenol red thread test), tear film breakup time (BUT), fluorescein staining (FL), corneal epithelial status (light microscopy), ultrastructure of corneal epithelial cells (electron microscopy), and expression levels of inflammatory cytokines (IL-1ß, TNF-α) in tears (enzyme-linked immunosorbent assay). Additionally, mRNA and protein expression levels of MMP-9, IL1ß, IL6, TNF-α, IFN-γ, and caspase-3 in corneal tissues were quantified (real-time quantitative PCR and Western blotting). Compared to the control group, the model group rats exhibited significant decreases in blink frequency (P < 0.001), tear secretion (Schirmer I test) values (P < 0.001), and tear film breakup time levels (P < 0.001). There was also a significant increase in fluorescein staining scores (P < 0.001) in the model group. Histological examination revealed distinct differences of the corneal epithelium between groups. The corneal epithelium of the model group appeared thicker, with disorganized cell arrangement in the superficial and basal layers, partial defects or detachment of superficial epithelial cells, and a rough, uneven surface. Scanning electron microscopy observations showed a rough corneal epithelial surface with numerous cracks and scattered vesicular-like structures in the model group. Furthermore, the model group rats exhibited a significant increase in expression of IL-1ß and TNF-α in tears (P < 0.001), and upregulated expression levels of MMP-9, TNF-α, IL-1ß, caspase-3, IL-6, and IFN-γ at both the mRNA and protein levels in corneal tissues (P < 0.001). In conclusion, the modified "wire-meshing cylindrical board" model effectively overcomes the limitations of the traditional "jogging board " dry eye model and successfully simulates the etiology of prolonged visual fatigue. This innovative EDE model demonstrates a high degree of relevance to dry eye conditions resulting from prolonged visual tasks, with a high success rate of model induction. Moreover, it proves to be a simple, practical, and easily replicable model, making it highly suitable for further studies on prolonged visual fatigue and facilitating its widespread adoption in research and clinical applications.

Water quality pollution assessment and source apportionment of lake wetlands: A case study of Xianghai Lake in the Northeast China Plain.

Surface water pollution has always posed a serious challenge to water quality management. Improving water quality management requires figuring out how to comprehend water quality conditions scientifically and effectively as well as quantitatively identify regional pollution sources. In this study, Xianghai Lake, a typical lake-type wetland on the Northeast China Plain, was taken as the research area. Based on a geographic information system (GIS) method and 11 water quality parameters, the single-factor evaluation and comprehensive water quality index (WQI) methods were used to comprehensively evaluate the water quality of the lake-type wetland in the level period. Four key water quality parameters were determined by the principal component analysis (PCA) method, and more convenient comprehensive water quality evaluation models, the minimum WQI considering weights (WQImin-w) and the minimum WQI without considering weights (WQImin-nw) were established. The multiple statistical method and the absolute principal component score-multiple liner regression (APCS-MLR) model were combined to analyse the lake pollution sources based on the spatial changes in pollutants. The findings demonstrated that the WQImin-nw model's water quality evaluation outcome was more accurate when weights were not taken into account. The WQImin-nw model can be used as a simple and convenient way to comprehend the variations in water quality in wetlands of lakes and reservoirs. It was concluded that the comprehensive water quality in the study area was at a "medium" level, and CODMn was the main limiting factor. Nonpoint source pollution (such as agricultural planting and livestock breeding) was the most important factor affecting the water quality of Xianghai Lake (with a comprehensive contribution rate of 31.65%). The comprehensive contribution rates of sediment endogenous and geological sources, phytoplankton and other plants, and water diversion and other hydrodynamic impacts accounted for 25.12%, 19.65%, and 23.58% of the total impact, respectively. This study can provide a scientific method for water quality assessment and management of lake wetlands, and an effective support for migration of migratory birds, habitat protection and grain production security.

Sec61γ is a vital protein in the endoplasmic reticulum membrane promoting tumor metastasis and invasion in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most common malignant tumors worldwide. Finding effective prognostic markers and therapeutic targets is of great significance for controlling metastasis and invasion clinically. METHODS: The open copy-number aberrations and gene expression datasets were analysed, and the data of 102 LUAD patients was used for further validation. The cell proliferation, colony formation, migration, invasion assays and mice tumor models were used to detect the function of SEC61G. The epidermal growth factor receptor (EGFR) pathway was also detected to find the mechanism of Sec61γ. RESULTS: Based on the open datasets, we found that the high level of SEC61G mRNA may drive LUAD metastasis. Furthermore, the overexpression of Sec61γ protein was significantly associated with poor prognosis and greater tumor cell proliferation and metastasis. The SEC61G knockdown could inhibit the EGFR pathway, including STAT3, AKT and PI3K, which can be reversed by Sec61γ overexpression and epithelial growth factor (EGF) supplement. CONCLUSIONS: Sec61γ promoted the proliferation, metastasis, and invasion of LUAD through EGFR pathways. Sec61γ might be a potential target for the treatment of LUAD metastases.

RNA-binding motif protein 10 represses tumor progression through the Wnt/ß- catenin pathway in lung adenocarcinoma.

RNA-binding motif protein 10 (RBM10), one of the members of the RNA-binding protein (RBP) family, has a tumor suppressor role in multiple cancers. However, the functional role of RBM10 in lung adenocarcinoma (LUAD) and the underlying molecular mechanism remains unclear. In this study, we observed that RBM10 is significantly downregulated in LUAD tissues compared with normal tissues. Low RBM10 expression is significantly associated with poor outcome of LUAD patients. In vitro and in vivo experiments show that RBM10 inhibits cell proliferation, metastasis and EMT progression in LUAD. Mechanistically, we demonstrate that RBM10 interacts with ß-catenin interacting protein 1 (CTNNBIP1) and positively regulates its expression, disrupting the binding of ß-catenin to the transcription factor TCF/LEF, thereby inactivating the Wnt/ß-catenin pathway. In conclusion, this is the first study reporting the role of RBM10 in suppressing LUAD progression at least via partly inactivating the Wnt/ß-catenin pathway, which provides new insights into the tumorigenesis and metastasis of LUAD. Thus, RBM10 may be a promising new therapeutic target or clinical biomarker for LUAD therapy in the future.

LncRNA NR2F2-AS1 induces epithelial-mesenchymal transition of non-small cell lung cancer by modulating BVR/ATF-2 pathway via regulating miR-545-5p/c-Met axis.

Non-small cell lung cancer (NSCLC) is one type of the most common cancers, which results in the major death worldwide. This study focuses on the understanding of the molecular mechanism of lncRNA NR2F2-AS1 and its regulation on epithelial-mesenchymal transition (EMT) in the development of NSCLC. Expressions of lncRNA NR2F2-AS1, miR-545-5p, c-Met, biliverdin reductase (BVR), ATF-2 and EMT-related markers in NSCLC tissues and cells were measured by western blotting and RT-qPCR assays. The impact of lncRNA NR2F2-AS1 and miR-545-5p on the cell proliferation, migration, invasion and EMT were analyzed by CCK-8, colony formation, wound healing and transwell assays. The interactions among lncRNA NR2F2-AS1, miR-545-5p and c-Met predicted by bioinformatic analysis were evaluated through dual luciferase reporter assay and fluorescence in situ hybridization (FISH). After generating tumor xenografts, immunohistochemistry was utilized to measure the expression of Ki-67 and EMT-related proteins in vivo. Our results showed that lncRNA NR2F2-AS1, c-Met, BVR and ATF-2 were overexpressed while miR-545-5p was silenced in NSCLC tissues and cells. Silencing of lncRNA NR2F2-AS1 or upregulating miR-545-5p significantly inhibited the cell proliferation, migration, invasion and EMT process. The EMT process could be inhibited by suppressing c-Met/BVR/ATF-2 axis. The tumor xenograft experiments demonstrated that the tumor growth and EMT process were significantly inhibited by silencing lncRNA NR2F2-AS1 or overexpression of miR-545-5p in vivo. LncRNA NR2F2-AS1 promoted the NSCLC development through suppressing miR-545-5p to activate EMT process through c-Met/BVR/ATF-2 axis. Our study indicated that lncRNA NR2F2-AS1 and miR-545-5p could be used as potential therapeutic targets to improve NSCLC treatment.

The value of AGR2 and KRT5 as an immunomarker combination in distinguishing lung squamous cell carcinoma from adenocarcinoma.

With the advancement of tumor subtype-specific treatments, precise histopathologic distinction between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) is of significant clinical importance. Nevertheless, the current markers are insufficiently precise in poorly differentiated tissue. This study aimed to establish a histology-specific immunomarker combination to subclassify non-small cell lung cancer (NSCLC) specimens. Based on previous work, we assessed the differential expression of anterior gradient 2 (AGR2) and keratin 5 (KRT5) in ADC and SCC by analyzing public datasets and postoperative specimens. Subsequently, we established a train set (n = 188) and a validation set (n = 42) comprised of NSCLC surgical specimens for training and verifying the subtype-identification capabilities of the two biomarkers separately and in combination, and contrasted the diagnostic utility of AGR2-KRT5 with that of the classic immunomarker combination, TTF1-P40. Differential expression of the two genes was statistically significant in ADC and SCC samples, both at the mRNA and protein levels. The specificity and sensitivity of AGR2 to detect ADC in the training set were 97.0% and 94.4%, while the sensitivity and specificity of KRT5 to determine SCC were 93.9% and 98.9%, respectively. The accuracies of AGR2-KRT5 in ADC, SCC, and across all samples were 93.3%, 92.0% and 92.6% respectively. In the validation cohort, the predictive accuracy of AGR2-KRT5 was up to 100% for ADC and 86.7% for SCC. Compared with TTF1-P40 in ADC samples, AGR2-KRT5 had 8.4% higher accuracy. In summary, the AGR2-KRT5 immunomarker combination reliably distinguished SCC from ADC, and was more accurate than TTF1-P40 in ADC.

High BASP1 Expression is Associated with Poor Prognosis and Promotes Tumor Progression in Human Lung Adenocarcinoma.

BASP1 is involved in signal transduction and cytoskeleton formation and plays a tumor-promoting or tumor-suppressing role in cancers. We found BASP1 was overexpressed in lung adenocarcinoma tissues and promoted the proliferation and migration of lung adenocarcinoma cells. The mechanism may be related to inhibition of cell apoptosis and abnormal activation of the Wnt/ß-catenin pathway and epithelial-mesenchymal transformation. BASP1 is associated with poor prognosis in lung adenocarcinoma.

Reference genome and annotation updates lead to contradictory prognostic predictions in gene expression signatures: a case study of resected stage I lung adenocarcinoma.

RNA-sequencing enables accurate and low-cost transcriptome-wide detection. However, expression estimates vary as reference genomes and gene annotations are updated, confounding existing expression-based prognostic signatures. Herein, prognostic 9-gene pair signature (GPS) was applied to 197 patients with stage I lung adenocarcinoma derived from previous and latest data from The Cancer Genome Atlas (TCGA) processed with different reference genomes and annotations. For 9-GPS, 6.6% of patients exhibited discordant risk classifications between the two TCGA versions. Similar results were observed for other prognostic signatures, including IRGPI, 15-gene and ORACLE. We found that conflicting annotations for gene length and overlap were the major cause of their discordant risk classification. Therefore, we constructed a prognostic 40-GPS based on stable genes across GENCODE v20-v30 and validated it using public data of 471 stage I samples (log-rank P < 0.0010). Risk classification was still stable in RNA-sequencing data processed with the newest GENCODE v32 versus GENCODE v20-v30. Specifically, 40-GPS could predict survival for 30 stage I samples with formalin-fixed paraffin-embedded tissues (log-rank P = 0.0177). In conclusion, this method overcomes the vulnerability of existing prognostic signatures due to reference genome and annotation updates. 40-GPS may offer individualized clinical applications due to its prognostic accuracy and classification stability.

Superadsorbent hydrogel based on lignin and montmorillonite for Cu(II) ions removal from aqueous solution.

Superadsorbent hydrogel was prepared from lignin and montmorillonite for Cu(II) ions removal, and the chemical structure and morphology of the hydrogel were characterized by FT-IR, XRD, SEM and XPS. The swelling kinetics of the prepared hydrogel was investigated, and the result showed that the swelling process fit the Schott second-order dynamic equation. The influences of pH, contact time, Na+ concentration, and initial Cu(II) ion concentration on adsorption were studied, and the maximum adsorption value was 1.17 mmol/g, and the adsorption was rapid during the initial 5 h period, and copper ions adsorption on the superadsorbent hydrogel is a favorable process. The results also indicated that the adsorption kinetics was in accordance with the pseudo-second-order kinetic model and the adsorption isotherm conformed to the Freundlich model. FT-IR and XPS analysis revealed that the adsorption behavior was mainly due to ion exchange. The desorption ratios of copper ions from the superadsorbent were >0.8, and the regeneration efficiency was >80% after five cycles reuse, and the results show the excellent desorption performance and reusability of the prepared hydrogel.

Sinoporphyrin Sodium-Mediated Sonodynamic Therapy Inhibits RIP3 Expression and Induces Apoptosis in the H446 Small Cell Lung Cancer Cell Line.

BACKGROUND/AIMS: Sonodynamic therapy (SDT) is expected to be a new method to solve the clinical problems caused by advanced metastasis in patients with lung cancer. The use of ultrasound has the advantage of being noninvasive, with deep-penetration properties. This study explored the anti-tumor effect of SDT with a new sonosensitizer, sinoporphyrin sodium (DVDMS), on the human small cell lung cancer H446 cell line in vitro and in vivo. METHODS: Absorption of DVDMS was detected by a fluorescence spectrophotometer, and DVDMS toxicity was determined using a Cell Counting Kit-8. Mitochondrial membrane potential (MMP) was assessed using the JC-1 fluorescent probe. Cell apoptosis was measured by flow cytometry, and apoptosis-related proteins were detected by western blotting. The expression of cytokines was measured using an enzyme-linked immunosorbent assay and quantitative real-time PCR. To verify the in vitro results, we detected tumor volumes and weight changes in a xenograft nude mouse model after DVDMS-SDT. Hematoxylin and eosin staining was used to observe changes to the tumor, heart, liver, spleen, lung, and kidney of the mice, and immunohistochemistry was used to examine changes in the expression of tumor CD34 and receptor-interacting protein kinase-3 (RIP3), while terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to observe apoptosis in tumor tissues. RESULTS: DVDMS-SDT-treated H446 cells increased the rate of cellular apoptosis and the levels of reactive oxygen species (ROS), cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, and caspase-10, and decreased the levels of MMP, RIP3, B-cell lymphoma 2, vascular endothelial growth factor, and tumor necrosis factor-α. The sonotoxic effect was mediated by ROS and was reduced by a ROS scavenger (N-acetyl-L-cysteine). In the in vivo mouse xenograft model, DVDMS-SDT showed efficient anti-cancer effects with no visible side effects. CONCLUSION: DVDMS-SDT induced apoptosis in H446 cells, in part by targeting mitochondria through the mitochondria-mediated apoptosis signaling pathway, and the extrinsic apoptosis pathway was also shown to be involved. Both apoptosis and changes in RIP3 expression were closely related to the generation of ROS. DVDMS-SDT will be advantageous for the management of small cell lung cancer due to its noninvasive characteristics.