Distant metastasis is the major cause of cancer-related deaths in patients with lung adenocarcinoma (LAD). Emerging evidence reveals that miRNA is critical for tumor metastasis. miR-214 expression ...has been associated with LAD progression. However, whether and how miR-214 is involved in the development and metastasis of LAD remain unaddressed. Here, we found that the expression of miR-214 was elevated in LAD and correlated positively with LAD metastasis and epithelial-mesenchymal transition (EMT). In addition, we found that miR-214 enhanced the molecular program controlling the EMT of LAD cells and promoted LAD cell metastasis both in vitro and in vivo. This study thus provides the first evidence to show that the miR-214 expression by LAD cells contributes to the EMT and metastasis of LAD. Mechanistically, Sufu was identified as an important miR-214 functional target for the EMT and metastasis of LAD, ectopic expression of Sufu alleviated miR-214 promoted EMT and metastasis. Importantly, the expression of Sufu inversely correlated with the expression of miR-214 and vimentin and positively associated with the expression of E-cadherin in the tumor cells from human LAD patients. Collectively, this study uncovers a previously unappreciated miR-214-Sufu pathway in controlling EMT and metastasis of LAD and suggests that interfering with miR-214 and Sufu could be a viable approach to treat late stage metastatic LAD patients.
Studies have demonstrated that the regulatory role of competitive endogenous RNA (ceRNA) networks is closely related to tumorigenesis, which provides new targets for tumor therapy. In this study, the ...focus was to explore the ceRNA networks that regulate
expression and their prognosis in non-small cell lung cancer (NSCLC).
Firstly, the Cancer Genome Atlas (TCGA) data combined with immunohistochemical staining was used to compare
expression in NSCLC tissues and normal tissues. Thereafter, samples from the immunohistochemical staining of NSCLC were integrated with clinical follow-up data for prognostic analysis. The Starbase database was employed to search for
-targeted miRNAs and lncRNAs, and survival analysis was performed using clinical data from TCGA to obtain
expression and prognosis-related ceRNA networks. Finally, the prognostic and therapeutic prospects of
in NSCLC were further analyzed from methylation sites and the immune microenvironment.
The study results revealed that
was significantly overexpressed in NSCLC tissues compared to normal tissues, and clinical follow-up data showed that the overexpression group was associated with poor prognosis. In addition, the Starbase data combined with TCGA clinical data analysis demonstrated that the AL513318.2/hsa-miR-26a-5p/
network regulates
overexpression in NSCLC and is associated with poor prognosis. Methylation analysis revealed that 11 methylation sites were closely associated with the prognosis of NSCLC. In addition, the immune prognostic risk model showed that the high-risk group was associated with a poorer prognosis than the low-risk group, despite showing a better immunotherapy outcome.
In summary, the AL513318.2/hsa-miR-26a-5p/
network upregulates
expression in NSCLC and is associated with poor prognosis. Therefore it may be a prognostic biomarker of NSCLC and a potential therapeutic target.
Airborne (or satellite) gravity measurement is a commonly used remote sensing method to obtain the underground density distribution. Airborne gravity gradiometry data have a higher horizontal ...resolution to shallower causative sources than airborne gravity anomaly, so joint exploration of airborne gravity and its gradient data can simultaneously obtain the anomaly feature of sources with different depths. The most commonly used joint inversion method of gravity and its gradient data is the data combined method, which is to combine all the components into a data matrix as mutual constraints to reduce ambiguity and non-uniqueness. In order to obtain higher resolution results, we proposed a cooperate density-integrated inversion method of airborne gravity and its gradient data, which firstly carried out the joint inversion using cross-gradient constraints to obtain two density structures, and then fused two recovered models into a result through Fourier transform; finally, data combined joint inversion of airborne gravity, and gradient data were reperformed to achieve high-resolution density result using fused density results as a reference model. Compared to the data combined joint inversion method, the proposed cooperate density-integrated inversion method can obtain higher resolution and more accurate density distribution of shallow and deep bodies meanwhile. We also applied it to real data in the mining area of western Liaoning Province, China. The results showed that the depth of the skarn-type iron mine in the region is about 900–1300 m and gives a more specific distribution compared to the geological results, which provided reliable data for the next exploration plan.
Flap endonuclease 1 (FEN1) plays a crucial role in both DNA replication and damage repair. In this study, FEN1 expression and its clinical-pathologic significance in non–small-cell lung cancer ...(NSCLC) was investigated. Quantitative RT-PCR and immunohistochemistry analysis identified that both FEN1 mRNA and protein were highly overexpressed in about 36% of 136 cancer tissues compared to adjacent tissues, in which FEN1 was generally undetectable. Notably, patients with FEN1-overexpressed cancers were prone to have poor differentiation and poor prognosis. A strong positive correlation between the levels of FEN1 and Ki-67 staining was identified in these NSCLC tissues (r = 0.485), suggesting overexpressed FEN1 conferred a proliferative advantage to NSCLC. Furthermore, knockdown of FEN1 resulted in G1/S or G2/M phase cell cycle arrest and suppressed in vitro cellular proliferation in NSCLC cancer cells. Consistently, a selective FEN1 inhibitor was shown to effectively inhibit cellular proliferation of NSCLC cells in a dose-dependent manner. Additionally, knockdown of FEN1 significantly attenuated homologous DNA repair efficiency and enhanced cytotoxic effects of cisplatin in NSCLC cells. Taken together, these findings have indicated that overexpressed FEN1 represents a prognostic biomarker and potential therapeutic target for NSCLC treatment, which warrants further study.
For several classes of decisions, the use of target-based decision analysis (TBDA) is more appropriate than utility analysis. Recent literature on TBDA mainly focuses on different expression forms of ...targets and performance levels, and on different types of aggregation operators in terms of multi-attribute preference functions. However, different expression forms are usually introduced separately in literature, which cannot fully support the inherent complexity of problems along with different perception and knowledge levels of decision makers during assessing targets and performance levels. Furthermore, although there are attractive features of multilinear target-based preference functions (MTPFs), its applications are seldom considered because of the complexity of identifying their coefficients. In order to solve these two issues, an integrated approach is proposed for multilinear hybrid-information target-based decision analysis, which can deal with diverse forms of targets and performance levels, and identify the coefficients of MTPFs. First, given targets and performance levels for each attribute being expressed in multiple forms simultaneously, a generalized procedure is proposed to transform different forms into probability distributions, and to measure probability of target achievement for each attribute. Second, a novel procedure to identify the coefficients of MTPFs is proposed. This procedure is based on the multilinear model and 2-additive fuzzy measures, which is based on the equivalence between multilinear model based on fuzzy measures and MTPFs. The approach is applied to a case study involving customer competitive evaluation of smart thermometer patches to demonstrate its feasibility and advantages.
The composition of the intestinal microbiome varies considerably between individuals and is correlated with health
. Understanding the extent to which, and how, host genetics contributes to this ...variation is essential yet has proved to be difficult, as few associations have been replicated, particularly in humans
. Here we study the effect of host genotype on the composition of the intestinal microbiota in a large mosaic pig population. We show that, under conditions of exacerbated genetic diversity and environmental uniformity, microbiota composition and the abundance of specific taxa are heritable. We map a quantitative trait locus affecting the abundance of Erysipelotrichaceae species and show that it is caused by a 2.3 kb deletion in the gene encoding N-acetyl-galactosaminyl-transferase that underpins the ABO blood group in humans. We show that this deletion is a ≥3.5-million-year-old trans-species polymorphism under balancing selection. We demonstrate that it decreases the concentrations of N-acetyl-galactosamine in the gut, and thereby reduces the abundance of Erysipelotrichaceae that can import and catabolize N-acetyl-galactosamine. Our results provide very strong evidence for an effect of the host genotype on the abundance of specific bacteria in the intestine combined with insights into the molecular mechanisms that underpin this association. Our data pave the way towards identifying the same effect in rural human populations.
Due to the widespread presence and harmfulness of heavy metals in the environment, scholars around the world have evaluated the exposure characteristics and health risks of heavy metals. To ...understand the status, hotspots, and development treads of heavy metal health risk assessment research, we used bibliometric analysis tools to conduct scientometric analysis of the literature related to the health risk assessment of heavy metals in the Web of Science database from 2000 to 2022. The analysis results indicate that research related to heavy metal health risk assessment is rapidly developing in both developed and developing countries. China’s significant international influence in this field is worth noting, as there are many publications and highly cited documents related to China. France and other developed countries also play an important role in this field due to their high centrality and strong bursts. The results of co-citation cluster analysis and keyword co-occurrence analysis indicate that in the past two decades, the primary research domains and hotspots of heavy metal health risk assessment have been the study of heavy metals in soil, dust, drinking water, vegetables, fish, and sediment. There is a specific focus on bioaccumulation, bioavailability, source apportionment, and spatial distribution of heavy metals. The main types of heavy metals studied are lead, cadmium, mercury, and zinc. The results of the bursts keywords analysis suggest that future research trends may focus more on the health risks of heavy metals in different functional areas of cities.
Surface vegetation represents a link between the atmosphere, water, and human society. The quality of the ecological environment in the upper and middle reaches of the Yellow River (UMRYR) has a ...direct impact on the downstream basin. However, only few studies have investigated vegetation changes in the UMRYR. Therefore, we used the coefficient of variation and linear regression analyses to investigate spatiotemporal variations in the normalized difference vegetation index (NDVI). Further, we used the geographical detector model (GDM) to determine the spatial heterogeneity of the NDVI and its driving factors and then investigated the factors driving the spatial distribution of the NDVI in different climatic zones and vegetation types. The results showed that the NDVI in the UMRYR was high during the study period. The NDVI was distributed in a spatially heterogeneous manner, and it decreased from the southeast to the northwest. We observed severe degradation in the southeast, mild degradation in the northwest and the Yellow River source region, and substantial vegetation recovery in the central basin. Precipitation and vegetation type drove the spatial distribution of the NDVI. Natural factors had higher influence than that of anthropogenic factors, but the interactions between the natural and anthropogenic factors exhibited non-linear and bivariate enhancements. Inter-annual variations in precipitation were the main natural factor influencing inter-annual NDVI variations, while precipitation and anthropogenic ecological restoration projects jointly drove NDVI changes in the UMRYR. This study provides a better understanding of the current status of the NDVI and mechanisms driving vegetation restoration in the UMRYR.
It is very appealing to synthesize functional soft materials from natural and abundant plant diterpenes because they have conformationally rigid and chiral properties. Herein, dehydroabietic-based ...monoamide (DA-1) and diamide (DA-2) were designed by introducing device interactions, π–π stacking and hydrogen bonding, with an aromatic group, CO, and N–H. DA-1 and DA-2 can be gelled in a mixed solvent and a single solvent, respectively. Several novel supramolecular organic gels including highly entangled three-dimensional networks composed of rods or fibers were constructed. Interestingly, DA-2 forms a helical structure that is right-handed under the cooperative control of the solvent and the rigid structure of rosin. Gel formation was primarily driven by hydrogen bonding, π–π stacking, and van der Waals force. Combined with Gaussian calculation and X-ray diffraction (XRD), we established pack patterns for each system, revealing the roles played by rosin and amide groups. Moreover, the carbon tetrachloride gel of DA-2 can effectively remove Congo red in an aqueous solution, and the removal rate can reach 98.4%. This research explores an efficient organic gel for adsorbing Congo red dye with the secretions of pine trees.
This study aimed to identify the specimen type that has high positivity and its proper sampling time for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing to promote diagnostic ...efficiency. All SARS-CoV-2-infected patients with a laboratory-confirmed diagnosis in Zhoushan City were followed up for viral shedding in respiratory tract specimens and faecal samples. Positivity was analysed both qualitatively and quantitatively by proper statistical approaches with strong testing power. Viral shedding in respiratory tract and faecal specimens was prolonged to 45 and 40 days after the last exposure, respectively. The overall positive rate in respiratory tract specimens was low and relatively unstable, being higher in the early-to-mid stage than in the mid-to-late stage of the disease course. Compared with respiratory tract specimens, faecal samples had a higher viral load, higher overall positive rate, and more stable positivity in different disease courses and varied symptomatic status. Faecal specimens have the potential ability to surpass respiratory tract specimens in virus detection. Testing of faecal specimens in diagnosis, especially for identifying asymptomatic carriers, is recommended. Simultaneously, testing respiratory tract specimens at the early-to-mid stage is better than testing at the mid-to-late stage of the disease course. A relatively small sample size was noted, and statistical approaches were used to address it. Information was missing for both specimen types at different stages of the disease course due to censored data. Our research extends the observed viral shedding in both specimen types and highlights the importance of faecal specimen testing in SARS-CoV-2 diagnosis. Healthcare workers, patients, and the general public may all benefit from our study findings. Disposal of sewage from hospitals and residential areas should be performed cautiously because the virus sheds in faeces and can last for a long time.