Differential expression and clinical significance of long non-coding RNAs in the development and progression of lung adenocarcinoma.

With the development of gene testing technology, we have found many different genes, and lncRNA is one of them. LncRNAs refer to a non-protein coding RNA molecule with a length of more than 200bp, which is one of the focuses of research on human malignant diseases such as LUAD. LncRNAs act as an oncogene or inhibitor to regulate the occurrence and progression of tumors. The differential expression of LncRNAs promotes or inhibits the progression of lung adenocarcinoma by affecting cell proliferation, metastasis, invasion, and apoptosis, thus affecting the prognosis and survival rate of patients. Therefore, LncRNAs can be used as a potential target for diagnosis and treatment of cancer. The early diagnosis of the disease was made through the detection of tumor markers. Because lung adenocarcinoma is not easy to diagnose in the early stage and tumor markers are easy to ignore, LncRNAs play an important role in the diagnosis and treatment of lung adenocarcinoma. The main purpose of this article is to summarize the known effects of LncRNAs on lung adenocarcinoma, the effect of differential expression of LncRNAs on the progression of lung adenocarcinoma, and related signal transduction pathways. And to provide a new idea for the future research of lung adenocarcinoma-related LncRNAs.

Photodegradation and van der Waals Passivation of Violet Phosphorus.

Violet phosphorus (VP), a novel two-dimensional (2D) nanomaterial, boasts structural anisotropy, a tunable optical bandgap, and superior thermal stability compared with its allotropes. Its multifunctionality has sparked widespread interest in the community. Yet, the VP's air susceptibility impedes both probing its intrinsic features and device integration, thus making it of urgent significance to unveil the degradation mechanism. Herein, we conduct a comprehensive study of photoactivated degradation effects on VP. A nitrogen annealing method is presented for the effective elimination of surface adsorbates from VP, as evidenced by a giant surface-roughness improvement from 65.639 nm to 7.09 nm, enabling direct observation of the intrinsic morphology changes induced by photodegradation. Laser illumination demonstrates a significant thickness-thinning effect on VP, manifested in the remarkable morphological changes and the 73% quenching of PL intensity within 160 s, implying its great potential for the efficient selected-area etching of VP at high resolution. Furthermore, van der Waals passivation of VP using 2D hexagonal boron nitride (hBN) was achieved. The hBN-passivated channel exhibited improved surface roughness (0.512 nm), reduced photocurrent hysteresis, and lower responsivity (0.11 A/W @ 450 nm; 2 µW), effectively excluding adsorbate-induced electrical and optoelectrical effects while disabling photodegradation. Based on our experimental results, we conclude that three possible factors contribute to the photodegradation of VP: illumination with photon energy higher than the bandgap, adsorbed H2O, and adsorbed O2.

Bacillus subtilis improves antioxidant capacity and optimizes inflammatory state in broilers.

OBJECTIVE: Bacillus subtilis, a kind of probiotic with broad-spectrum antibacterial function, was commonly used in livestock and poultry production. Recent research suggested that Bacillus subtilis may have antioxidant properties and improve immune response. This study aimed to verify the probiotic function of Bacillus subtilis in the production of broiler chickens. METHODS: A total of 324 (1-day-old) Arbor Acres broilers were selected and randomly divided into three groups: basal diet group (Ctr Group), basal diet + antibiotic growth promoter group (Ctr + AGP) and basal diet + 0.5% Bacillus subtilis preparation group (Ctr + Bac). The experiment lasted for 42 days. Muscle, serum and liver samples were collected at 42 days for determination. RESULTS: The results showed that Bacillus subtilis could decrease malondialdehyde content in the serum and liver (p<0.05) and increase superoxide dismutase 1 mRNA expression (p<0.01) and total superoxide dismutase (p<0.05) in the liver. In addition, compared with AGP supplementation, Bacillus subtilis supplementation increased interleukin-10 (IL-10) and decreased tumor necrosis factor-α and IL-1ß level in the serum (p<0.05). At 45 minutes after slaughter Ctr + Bac presented a higher a* value of breast muscle than Ctr Group (p<0.05), while significant change in leg muscle was not identified. Moreover, there was no difference in weight, shear force, cooking loss and drip loss of breast and leg muscle between treatments. CONCLUSION: Our results demonstrate that Bacillus subtilis in diet can enhance antioxidant capacity and optimize immune response of broilers.

Docosahexaenoic acid-mediated milk protein treated by ultrasound-assisted pH shifting for enhanced astaxanthin delivery and processed cheese application.

Whey protein isolate (WPI)-based nanodelivery systems have recently attracted an increasing amount of attention. Despite this, research focusing on milk protein concentrate (MPC) and micellar casein (MCC) as carriers loaded in hydrophobic compounds is lacking. This study investigated the mediated effect of docosahexaenoic acid (DHA) in 3 different milk proteins for the embedding of astaxanthin (ASTA) after ultrasound-assisted pH-shifting treatment. We then evaluated the application of milk protein carriers in cheese processing by comparing MPC, MCC, and WPI. The particle size, polydispersity index, and zeta potential results of the milk protein-DHA complex suggested that the addition of 0.36 µmol/mL DHA optimized the delivery of milk protein to ASTA. All 3 DHA-mediated milk proteins induced an improvement in encapsulation efficiency and antioxidant properties of ASTA. Furthermore, the DHA-mediated MPC and MCC played a stronger role in improving the bioaccessibility and thermal and storage stability of ASTA than those without DHA. Tests conducted to examine the application in cheese production indicated that MCC carrier had a positive effect on the texture of cheeses. However, the delivery effect was dependent on the milk protein variety, and MCC exhibited the best protection ability of ASTA, followed by MPC and WPI. The simulated digestion and storage stability results of cheese further confirmed that the protein encapsulation mediated by DHA was more conducive to ASTA absorption. These findings suggested that the DHA-mediated milk protein complexes studied here may be suitable hydrophilic delivery carriers for the hydrophobic nutrient ASTA, potentially playing different roles in improving its storage stability and bioaccessibility.

Identifying the Environmental Determinants of Lung Cancer: A Case Study of Henan, China.

Lung cancer has become one of the most prevalent cancers in the last several decades. Studies have documented that most cases of lung cancer are caused by inhaling environmental carcinogens while how external environmental factors lead to individual lung cancer is still an open issue as the pathogenesis may come from the combined action of multiple environmental factors, and such pathogenic mechanism may vary from region to region. Based on the data of lung cancer cases from hospitals at the county level in Henan from 2016 to 2020, we analyzed the response relationship between lung cancer incidence and physical ambient factors (air quality, meteorological conditions, soil vegetation) and socioeconomic factors (occupational environment, medical level, heating mode, smoking behavior). We used a Bayesian spatio-temporal interaction model to evaluate the relative risk of disease in different regions. The results showed that smoking was still the primary determinant of lung cancer, but the influence of air quality was increasing year by year, with meteorological conditions and occupational environment playing a synergistic role in this process. The high-risk areas were concentrated in the plains of East and Central Henan and the basin of South Henan, while the low-risk areas were concentrated in the hilly areas of North and West Henan, which were related to the topography of Henan. Our study provides a better understanding of the environmental determinants of lung cancer which will help refine existing prevention strategies and recognize the areas where actions are required to prevent environment and occupation related lung cancer.

Two tales of platform regimes in China's food-delivery platform economy.

This article brings the often-overlooked concept of the labor regime back to the study of China's food-delivery platform workers. Two tales of platform regimes emerge: individualized platform despotism and bureaucratized platform despotism, which apply to crowdsourcing couriers and dedicated delivery couriers, respectively. This study compares these two types of platform regimes in terms of their institutional foundation and labor organization. Despite different institutional arrangements and labor organization, both types of food-delivery couriers belong to a despotic platform regime revealing workers' subordination to the platform. In conclusion, it discusses the implications and limitations of this study.

Analysis of Diabetes Clinical Data Based on Recurrent Neural Networks.

At present, diabetes is one of the most important chronic noncommunicable diseases, that have threatened human health. By 2020, the number of diabetic patients worldwide has reached 425 million. This amazing number has attracted the great attention of various countries. With the progress of computing technology, many mathematical models and intelligent algorithms have been applied in different fields of health care. 822 subjects were selected in this paper. They were divided into 389 diabetic patients and 423 nondiabetic patients. Each of the subjects included 41 indicators. Too many indicator variables would increase the computational effort and there could be a strong correlation and data redundancy between the data. Therefore, the sample features were first dimensionally reduced to generate seven new features in the new space, retaining up to 99.9% of the valid information from the original data. A diagnostic and classification model for diabetes clinical data based on recurrent neural networks were constructed, and particle swarm optimization (PSO) was introduced to optimise recurrent neural network's hyperparameters to achieve effective diagnosis and classification of diabetes.

Relational POI recommendation model combined with geographic information.

Point of interest (POI) recommendation is a popular personalized location-based service. This paper proposes a Geographic Personal Matrix Factorization (GPMF) model that makes effective use of geographic information from the perspective of the relationship between POIs and users. This model considers the role of geographic information from multiple perspectives based on the locational relationship among users, the distributional relationship between users and POIs, and the proximity and clustering relationship among POIs. The GPMF mines the influence of geographic information on different objects and carries out unique modeling through cosine similarity, non-linear function, and k nearest neighbor (KNN). This study explored the influence of geographic information on POI recommendation through extensive experiments with data from Foursquare. The result shows that GPMF performs better than the commonly used POI recommendation algorithm in terms of both precision and recall. Geographic information through proximity relations effectively improves the recommendation algorithm.

[Driving Mechanism of the Spatiotemporal Evolution of Vegetation in the Yellow River Basin from 2000 to 2020].

The NDVI (normalized difference vegetation index) was used as the vegetation coverage index. Based on the NDVI and weather data from 2000 to 2020, the characteristics of the spatiotemporal evolution and the driving mechanism of vegetation were investigated by using correlation analysis, the Theil-Sen estimator, the Mann-Kendall method, and multivariate residual trend analysis. The results showed that the growing season average NDVI in the Yellow River basin was a fluctuating upward trend of 0.005 a-1 from 2000 to 2020. Areas with significantly improved vegetation in the basin were mainly distributed in the Qinling Mountains, the Northern Shaanxi Plateau, and the Lvliang Mountains in the midstream. The average value of the partial correlation coefficient between the growing season average NDVI and rainfall in the Yellow River basin was 0.57, and the average value of the partial correlation coefficient between the growing season average NDVI and temperature was 0.49. The impact of rainfall on vegetation was higher than that of temperature. The areas where human activities significantly improved vegetation growth were mainly distributed in the northern Shaanxi Plateau, the Lvliang Mountains, and southern Ningxia. The areas where human activities inhibited vegetation growth were mainly distributed in cities with strong human activities such as Yinchuan, Baotou, Xi'an, Luoyang, Zhengzhou, and Taiyuan. Human activities and climate change contributed to 72% and 28% of the vegetation change in the Yellow River basin. Driven by human activities and climate change, the area where vegetation growth has improved in the Yellow River basin accounted for 96.4% of the basin area, of which the contribution rate of human activities greater than 80% of the area accounted for 34.3%, which was mainly distributed in the middle and southeast of the basin. The area with a contribution rate of climate change greater than 80% accounted for 4.2%, which was mainly distributed in the Sichuan-Tibet Plateau and Longzhong Loess Plateau in the basin. The results of this research can provide scientific support for the ecological protection and high-quality development of the Yellow River basin.

Short-term effects of indoor and outdoor air pollution on the lung cancer morbidity in Henan Province, Central China.

Lung cancer is one of the most common cancer types and a major cause of death. The relationship between lung cancer morbidity and exposure to air pollutants is of particular concern. However, the relationship and difference in lung cancer morbidity between indoor and outdoor air pollution effects remain unclear. In this paper, the aim was to comprehensively investigate the spatial relationships between the lung cancer morbidity and indoor-outdoor air pollution in Henan based on the standard deviation ellipse, spatial autocorrelation analysis and GeoDetector. The results indicated that (1) the spatial distribution of lung cancer morbidity was related to the geomorphology, while high-morbidity areas were concentrated in the plains and basins of Central, Eastern and Southern Henan. (2) Among the selected outdoor air pollutants, PM2.5, NO2, SO2, O3 and CO were significantly correlated with the lung cancer morbidity. The degree of indoor air pollution was measured by the use of heating energy, and the proportions of coal-heating households, households with coal/biomass stoves and households with heated kangs were highly decisive in regard to the lung cancer morbidity. (3) The interaction between two factors was more notable than a single factor in explaining the lung cancer morbidity. Moreover, the interaction type was mainly nonlinear enhancement, and the proportion of households with coal/biomass stoves imposed the strongest interaction effect on the other factors.

Differential expression of long non-coding RNAs as diagnostic markers for lung cancer and other malignant tumors.

Due to advances in chip and sequencing technology, several types and numbers of long non-coding RNAs (lncRNAs) have been identified. LncRNAs are defined as non-protein-coding RNA molecules longer than 200 nucleotides, and are now thought as a new frontier in the study of human malignant diseases including NSCLC. Diagnosis of numerous malignant tumors has been closely linked to the differential expression of certain lncRNAs. LncRNAs are involved in gene expression regulation at multiple levels of epigenetics, transcriptional regulation, and post-transcriptional regulation. Mutations, deletions, or abnormal expression levels lead to physiological abnormalities, disease occurrence and are closely associated with human tumor diseases. LncRNAs play a crucial role in cancerous processes as either oncogenes or tumor suppressor genes. The expression of lncRNAs can regulate tumor cell in the proliferation, migration, apoptosis, cycle, invasion, and metastasis. As such, lncRNAs are potential diagnostic and treatment targets for cancer. And that, tumor biomarkers need to be detectable in easily accessible body samples, should be characterized by high specificity and sufficient sensitivity. Herein, it is significant clinical importance to screen and supplement new biomarkers for early diagnosis of lung cancer. This study aimed at systematically describing lncRNAs from five aspects based on recent studies: concepts, classification, structure, molecular mechanism, signal pathway, as well as review lncRNA implications in malignant tumor.

Cross-neutralization of RBD mutant strains of SARS-CoV-2 by convalescent patient derived antibodies.

BACKGROUND: The emergence of COVID-19 pandemic resulted in an urgent need for the development of therapeutic interventions. Of which, neutralizing antibodies play a crucial role in the prevention and resolution of viral infection. METHODS: We generated antibody libraries from 18 different COVID-19 recovered patients and screened neutralizing antibodies to SARS-CoV-2 and its mutants. After 3 rounds of panning, 456 positive phage clones were obtained with high affinity to RBD (receptor binding domain). Clones were then reconstituted into whole human IgG for epitope binning assay and all 19 IgG were classified into 6 different epitope groups or Bins. RESULTS: Although all antibodies were found to bind RBD, the antibodies in Bin2 had superior inhibitory ability of the interaction between spike protein and angiotensin converting enzyme 2 receptor (ACE2). Most importantly, the antibodies from Bin2 showed stronger binding affinity or ability to mutant RBDs (N501Y, W463R, R408I, N354D, V367F, and N354D/D364Y) derived from different SARS-CoV-2 strains as well, suggesting the great potential of these antibodies in preventing infection of SARS-CoV-2 and its mutations. Furthermore, such neutralizing antibodies strongly restricted the binding of RBD to hACE2 overexpressed 293T cells. Consistently, these antibodies effectively neutralized wildtype and more transmissible mutant pseudovirus entry into hACE2 overexpressed 293T cells. In Vero-E6 cells, one of these antibodies can even block the entry of live SARS-CoV-2 into cells at 12.5 nM. CONCLUSIONS: These results indicate that the neutralizing human antibodies from the patient-derived antibody libraries have the potential to fight SARS-CoV-2 and its mutants in this global pandemic.

Critical role of Syk-dependent STAT1 activation in innate antiviral immunity.

The JAK/STAT1 pathway is generally activated by cytokines, providing essential antiviral defense. Here, we identify that STAT1 activation is independent of cytokines and JAKs at the early infection stage of some viruses, including influenza A virus (IAV). Instead, STAT1 is activated mainly through spleen tyrosine kinase (Syk) downstream of retinoic acid-inducible gene-I/mitochondrial antiviral-signaling protein (RIG-I/MAVS) signaling. Syk deletion profoundly impairs immediate innate immunity, as evidenced by the finding that Syk deletion attenuates tyrosine phosphorylation of STAT1 and reduces the expressions of interferon-stimulated genes (ISGs) in vitro and in vivo. The antiviral response to IAV infection is also significantly suppressed in the STAT1Y701F knockin mice. The results demonstrate that STAT1 activation is dependent on Syk rather than the cytokine-activated JAK signaling at the early stage of viral infection, which is critical for initial antiviral immunity. Our finding provides insights into the complicated mechanisms underlying host immune responses to viral infection.

Circ-FOXM1 knockdown suppresses non-small cell lung cancer development by regulating the miR-149-5p/ATG5 axis.

Circular RNAs (circRNAs) have been reported to be related to the development of human cancers. However, the function of circ-FOXM1 in non-small cell lung cancer (NSCLC) was largely unknown. Here, we revealed the role and functional mechanism of circ-FOXM1 in NSCLC progression. The relative expression of circ-FOXM1, microRNA-149-5p (miR-149-5p), and autophagy-related 5 (ATG5) was determined by quantitative real-time polymerase chain reaction (RT-qPCR). Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assay were employed to assess cell viability, apoptosis, and migration, respectively. The relative protein expression was detected by western blot. Furthermore, mouse xenograft was carried out to analyze the effect of circ-FOXM1 on tumor growth in vivo. In addition, the interaction between miR-149-5p and circ-FOXM1 or ATG5 was predicted by Starbase3.0 and confirmed by the dual-luciferase reporter assay and RNA pull-down assay. Circ-FOXM1 and ATG5 levels were upregulated, while the miR-149-5p level was downregulated in NSCLC tissues and cells. Circ-FOXM1 knockdown suppressed NSCLC cell viability, migration, and autophagy, and induced cell apoptosis. Interestingly, circ-FOXM1 targeted miR-149-5p to upregulate the ATG5 level. Moreover, circ-FOXM1 exerted function through repressing miR-149-5p expression, and miR-149-5p exerted function via inhibiting ATG5 expression. Our results suggested that circ-FOXM1 knockdown attenuated the development of NSCLC through modulating the miR-149-5p/ATG5 axis, providing a theoretical basis for the therapy of NSCLC.

Circ_100565 promotes proliferation, migration and invasion in non-small cell lung cancer through upregulating HMGA2 via sponging miR-506-3p.

BACKGROUND: Circular RNAs (circRNAs) play a vital role in the development of various cancers. Circ_100565 was found to be a highly expressed circRNA in non-small cell lung cancer (NSCLC) tissues screened by microarray profiles of circRNAs. However, the role of circ_100565 in NSCLC still remains unknown. METHODS: Microarray analysis was used to screen for differentially expressed circRNAs in NSCLC tissues. The expression levels of circ_100565, microRNA-506-3p (miR-506-3p) and high mobility group AT-hook 2 (HMGA2) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was detected by cell counting kit-8 (CCK-8) and colony formation assays. Transwell assay was used to determine the migration and invasion of cells. Besides, Western blot (WB) analysis was performed to assess the levels of proliferation and metastasis-related proteins and HMGA2 protein. Moreover, animal experiments were used to confirm the effect of circ_100565 on NSCLC tumor growth in vivo. In addition, the interaction between miR-506-3p and circ_100565 or HMGA2 was confirmed by dual-luciferase reporter, RNA immunoprecipitation (RIP) assay or biotin-labeled pull-down assay. RESULTS: Circ_100565 was upregulated in NSCLC, and its high expression was positively associated with the poor overall survival of NSCLC patients. Silencing of circ_100565 suppressed the proliferation, migration and invasion of NSCLC cells in vitro and reduced the tumor growth of NSCLC in vivo. Circ_100565 could sponge miR-506-3p, and miR-506-3p could target HMGA2. Moreover, miR-506-3p inhibitor or HMGA2 overexpression could reverse the inhibition effect of circ_100565 knockdown on NSCLC progression. CONCLUSION: Circ_100565 increased HMGA2 expression to promote proliferation, migration and invasion in NSCLC via absorbing miR-506-3p. Our findings provided a new biomarker for NSCLC therapy.

Dehydroeffusol inhibits hypoxia-induced epithelial-mesenchymal transition in non-small cell lung cancer cells through the inactivation of Wnt/ß-catenin pathway.

Dehydroeffusol (DHE) is a phenanthrene compound that possesses anti-tumor activity. However, the effect of DHE on non-small cell lung cancer (NSCLC) has not been investigated previously. Therefore, the objective of our study was to explore the role of DHE in NSCLC and the underlying mechanism. Our results showed that DHE significantly inhibited the cell viability of A549 cells in a dose- and time-dependent manner under normoxic condition. Moreover, A549 cells were more sensitive to DHE under hypoxic condition compared with the A549 cells cultured in normoxic condition. Hypoxia-induced increased migration and invasion abilities were mitigated by DHE in A549 cells. Treatment of DHE caused increased E-cadherin expression and decreased N-cadherin expression in hypoxia-induced A549 cells. DHE also suppressed hypoxia-induced increase in both protein and mRNA levels of hypoxia inducible factor-1α (HIF-1α) expression in A549 cells. Furthermore, DHE inhibited hypoxia-induced activation of Wnt/ß-catenin pathway in A549 cells. The inhibitory effect of DHE on hypoxia-induced EMT was reversed by LiCl, which is an activator of Wnt/ß-catenin signaling pathway. In conclusion, these findings demonstrated that DHE prevented hypoxia-induced EMT in NSCLC cells by inhibiting the activation of Wnt/ß-catenin pathway, suggesting that DHE might serve as a therapeutic target for the NSCLC metastasis.

Shortest Path Algorithm in Dynamic Restricted Area Based on Unidirectional Road Network Model.

Accurate and fast path calculation is essential for applications such as vehicle navigation systems and transportation network routing. Although many shortest path algorithms for restricted search areas have been developed in the past ten years to speed up the efficiency of path query, the performance including the practicability still needs to be improved. To settle this problem, this paper proposes a new method of calculating statistical parameters based on a unidirectional road network model that is more in line with the real world and a path planning algorithm for dynamically restricted search areas that constructs virtual boundaries at a lower confidence level. We conducted a detailed experiment on the proposed algorithm with the real road network in Zhengzhou. As the experiment shows, compared with the existing algorithms, the proposed algorithm improves the search performance significantly in the condition of optimal path under the premise of ensuring the optimal path solution.

LINC01518 knockdown inhibits tumorigenicity by suppression of PIK3CA/Akt pathway in oesophageal squamous cell carcinoma.

LncRNA LINC01518 was previously reported to be upregulated in oesophageal squamous cell carcinoma (ESCC) tissues compared with normal tissues. However, there are no previous studies concerning the specific function and molecular mechanism of LINC01518 in ESCC. LINC01518 and miR-1-3p expression levels in ESCC cells were detected by qRT-PCR. Cell proliferation and apoptosis were evaluated by CCK-8 and flow cytometry analysis, respectively. The relationships between LINC01518, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA) and miR-1-3p were explored by luciferase reporter assay. The alteration of the PIK3CA/protein kinase B (Akt) pathway was examined by Western blot. We found that LINC01518 expression was upregulated and miR-1-3p expression was downregulated in ESCC cells. LINC01518 knockdown inhibited cell proliferation and promoted apoptosis in ESCC cells. In addition, LINC01518 functioned as a competing endogenous RNA (ceRNA) for miR-1-3p in ESCC cells and miR-1-3p downregulation blocked the effects of LINC01518 knockdown on cell proliferation and apoptosis in ESCC cells. Moreover, PIK3CA was identified as a target of miR-1-3p and LINC01518 knockdown inhibited the PIK3CA/Akt pathway by upregulating miR-1-3p in ESCC cells. In conclusion, LINC01518 knockdown inhibited tumorigenicity in ESCC cells by suppression of PIK3CA/Akt pathway through upregulating miR-1-3p.

Circular RNA ZFR accelerates non-small cell lung cancer progression by acting as a miR-101-3p sponge to enhance CUL4B expression.

BACKGROUND: Non-small-cell lung carcinoma (NSCLC) is the most common type of lung cancer. Circular RNA ZFR (circZFR) is an identified circular RNA (circRNA) that is correlated with cancer progression. However, the role of circZFR in NSCLC remains unknown. In the present study, we aimed to investigate the function of circZFR in NSCLC and the underlying mechanism. METHODS: The expression patterns of circZFR were determined using qRT-PCR in NSCLC samples and cell lines. The subcellular distribution of circZFR in NSCLC cells was analyzed by fluorescence in situ hybridization (FISH). Cell proliferation was examined utilizing the CCK-8 assay. Cell migration and invasion were evaluated using the Transwell assay. We used the bioinformatics software TargetScan and miRanda to predict circRNA-miRNA and miRNA-mRNA interactions. RESULTS: Our results showed that circZFR expressions were significantly upregulated in NSCLC tissues and cell lines. Knockdown of circZFR significantly inhibited the cell proliferation, migration and invasion of NSCLC cells in vitro. Furthermore, we demonstrated that circZFR acted as a sponge to absorb microRNA-101-3p (miR-101-3p) and promoted cullin 4B (CUL4B) expression. CONCLUSIONS: Collectively, our results demonstrated that circZFR exhibited a carcinogenic role by sponging miR-101-3p and regulating CUL4B expression in NSCLC. These findings provided evidence for understanding the role of circZFR in NSCLC tumourigenesis.

Thymidylate synthase gene variation is associated with the risk for conotruncal heart defects in Chinese population.

Conotruncal heart defects are considered to be one of the most common types of birth defect worldwide. Genetic disturbances in folate metabolism such as Thymidylate synthase may increase risk for conotruncal heart defects. We evaluated two common Thymidylate synthase polymorphisms, including the 28 bp tandem repeat in the promoter enhancer region of the 5'-untranslated region and the 6 bp deletion in the 3'-untranslated region, as risk factors of conotruncal heart defects including various subtypes of malformations, in a total of 193 mothers with conotruncal heart defect in offspring and 234 healthy controls in the Chinese population. Logistic regression analyses revealed that mothers who were homozygotes with deletion (-/-) had a 1.8-fold (odds ratio: 1.8; 95% confidence interval: 1.0-3.0, p = 0.040) increased risk for conotruncal heart defect in offspring, respectively, when compared with mothers carrying the wild type (+/+) genotype. Consistently, individuals carrying the genotype -/- of the Thymidylate synthase 6 bp deletion also had higher plasma homocysteine levels compared to the mothers carrying the genotype +/+ in the control and conotruncal heart defect groups (p = 0.006 and p = 0.004, respectively). However, our results showed that Thymidylate synthase 28 bp tandem repeat polymorphism was not associated with risk for conotruncal heart defect and plasma homocysteine level. In conclusion, our data suggest that the maternal Thymidylate synthase 6 bp deletion polymorphism might be associated with plasma homocysteine level and risk for conotruncal heart defect in offspring.