Colorectal cancer (CRC) is the fourth most common cause of cancer-related mortality worldwide. The tumor, node, metastasis (TNM) stage remains the standard for CRC prognostication. Identification of ...meaningful microRNA (miRNA) and gene modules or representative biomarkers related to the pathological stage of colon cancer helps to predict prognosis and reveal the mechanisms behind cancer progression.
We applied a systems biology approach by combining differential expression analysis and weighted gene co-expression network analysis (WGCNA) to detect the pathological stage-related miRNA and gene modules and construct a miRNA-gene network. The Cancer Genome Atlas (TCGA) colon adenocarcinoma (CAC) RNA-sequencing data and miRNA-sequencing data were subjected to WGCNA analysis, and the GSE29623, GSE35602 and GSE39396 were utilized to validate and characterize the results of WGCNA.
Two gene modules (Gmagenta and Ggreen) and one miRNA module were associated with the pathological stage. Six hub genes (COL1A2, THBS2, BGN, COL1A1, TAGLN and DACT3) were related to prognosis and validated to be associated with the pathological stage. Five hub miRNAs were identified to be related to prognosis (hsa-miR-125b-5p, hsa-miR-145-5p, hsa-let-7c-5p, hsa-miR-218-5p and hsa-miR-125b-2-3p). A total of 18 hub genes and seven hub miRNAs were predominantly expressed in tumor stroma. Proteoglycans in cancer, focal adhesion, extracellular matrix (ECM)-receptor interaction and so on were common pathways of the three modules. Hsa-let-7c-5p was located at the core of miRNA-gene network.
These findings help to advance the understanding of tumor stroma in the progression of CAC and provide prognostic biomarkers as well as therapeutic targets.
In this paper, Fe3O4@SiO2@γ-mercaptopropyltrimethoxysilane (γ-MPTS) magnetic nanoparticles was prepared and a new method of magnetic solid phase extraction (MSPE)-high performance liquid ...chromatography (HPLC)-inductively coupled plasma mass spectrometry (ICP-MS) was developed for the speciation of mercury including inorganic mercury (Hg2+), methylmercury (MeHg+) and phenylmercury (PhHg+) in environmental water, wastewater, tap water and fish samples. A rapid separation of three target mercury species was achieved in 8min by employing relatively high ratio of methanol in HPLC mobile phase. Various parameters affecting Fe3O4@SiO2@γ-MPTS-based MSPE of target mercury species have been investigated. Under the optimized conditions, the limits of detection for Hg2+, MeHg+ and PhHg+ were in the range of 0.49–0.74ngL−1. The intra- and inter-day relative standard deviations (n=5) were less than 9.0% and 12%, respectively. The developed MSPE-HPLC-ICP-MS method was validated by the speciation of mercury in the Certified Reference Material of DORM-2 dogfish as well as real-world samples including environmental water, wastewater, tap water and fish samples, and it has the advantages of simple operation, rapid separation, high sensitivity, high enrichment factor and is suitable for the analysis of mercury species in samples with complex matrix.
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•A method of MSPE-HPLC-ICP-MS was proposed for the speciation of Hg2+, MeHg+ and PhHg+.•HPLC separation of Hg2+, MeHg+ and PhHg+ was completed within 8min.•The developed method provided high EFs, short analysis time, low LODs and wide linear range.•It is suitable for speciation of trace/ultra-trace mercury in real samples with complex matrix.
The advent of SELEX (systematic evolution of ligands by exponential enrichment) technology has shown the ability to evolve artificial ligands with affinity and specificity able to meet growing ...clinical demand for probes that can, for example, distinguish between the target leukemia cells and other cancer cells within the matrix of heterogeneity, which characterizes cancer cells. Though antibodies are the conventional and ideal choice as a molecular recognition tool for many applications, aptamers complement the use of antibodies due to many unique advantages, such as small size, low cost, and facile chemical modification. This Minireview will focus on the novel applications of aptamers and SELEX, as well as opportunities to develop molecular tools able to meet future clinical needs in biomedicine.
Advantages of aptamers and SELEX in diverse research fields are summarized in this Minireview, along with some limitations and possible solutions to them. Furthermore described are future perspectives for aptamer modification with a near‐infinite number of molecular‐modulating elements that will result in more powerful tools in bioscience.
Based on the case of the national electronic identification card (New eID) policy in Taiwan, this study integrated the government’s components with a privacy calculus model to analyze factors which ...affect personal data disclosure intention. Partial least squares structural equation modeling (PLS-SEM) was used to analyze the survey data and explore how citizens balance benefits and risks associated with the New eID issue. The research results suggested that financial compensation, personalized services, and service compatibility can enhance cognition of privacy-related benefits of citizens, while this cognition will further increase willingness to authorize their personal data. Moreover, the impact of government elements on citizens’ willingness to authorize their personal information also has statistical backings. Citizens’ cognition of privacy-related risks, however, has no statistical effect within the model, which is contrary to findings from previous studies. The study attempted to make contributions to supplementing the connotation of an extant theoretical framework, and discussed the privacy-related questions concerning digital government.
We propose an online framework to detect cyberattacks on automatic generation control. A cyberattack detection algorithm is designed based on the approach of dynamic watermarking. The detection ...algorithm provides a theoretical guarantee of detection of cyberattacks launched by sophisticated attackers possessing extensive knowledge of the physical and statistical models of targeted power systems. The proposed framework is practically implementable, as it needs no hardware update on generation units. The efficacy of the proposed framework is validated in both four-area system and 140-bus system.
Objective
This study was undertaken to uncover the pathophysiologic role of discoidin domain receptor 2 (DDR‐2), a putative fibrillar collagen receptor, in inflammation promotion and joint ...destruction in rheumatoid arthritis (RA).
Methods
In synovial tissue from patients with RA and from mice with collagen antibody–induced arthritis (CAIA) (using Ddr2−/− and DBA/1 mice), gene and protein expression levels of DDR‐2, interleukin‐15 (IL‐15), and Dkk‐1 were measured by quantitative reverse transcription–polymerase chain reaction, Western blotting, and immunohistochemistry. Gene knockdown of DDR2 in human RA fibroblast‐like synoviocytes (FLS) was conducted via small interfering RNA. Interaction between the long noncoding RNA H19 and microRNA 103a (miR‐103a) was assessed in RA FLS using RNA pulldown assays. Cellular localization of H19 was examined using fluorescence in situ hybridization assays. Chromatin immunoprecipitation and dual luciferase reporter assays were applied to verify H19 transcriptional and posttranscriptional regulation by miR‐103a.
Results
DDR2 messenger RNA (mRNA) expression was significantly associated with the levels of IL‐15 and Dkk‐1 mRNA in the synovial tissue of RA patients (r2 = 0.2022–0.3293, all P < 0.05; n = 33) and with the serum levels of IL‐15 and Dkk‐1 in mice with CAIA (P < 0.05). In human RA FLS, activated DDR‐2 induced the expression of H19 through c‐Myc. Moreover, H19 directly interacted with and promoted the degradation of miR‐103a.
Conclusion
These results indicate a novel role for activated DDR‐2 in RA FLS, showing that DDR‐2 is responsible for regulating the expression of IL‐15 and Dkk‐1 in RA FLS and is involved in the promotion of inflammation and joint destruction during pathophysiologic development of RA. Moreover, DDR‐2 inhibition, acting through the H19–miR‐103a axis, leads to reductions in the inflammatory reaction and severity of joint destruction in mice with CAIA, suggesting that inhibition of DDR‐2 may be a potential therapeutic strategy for RA.
Subduction of oceanic lithosphere can cause crustal growth and destruction, but whether this balancing act is common in a single fossil convergent system has been unclear. Here we report ...geochronologic‐geochemical‐isotopic data on Mesozoic igneous rocks in the central‐eastern Gangdese arc. Our results reveal: (a) A coupling of magmatic arc migration toward the continent interior with a marked incompatible enrichment of sub‐arc mantle magma sources; (b) numerous Late Cretaceous adakites were generated via combined partial melting of both eroded forearc crust debris and subducted oceanic crust; (c) the truncation of forearc crust and extremely short arc‐suture distance. Our work demonstrates that although there was significant vertical growth of juvenile crust throughout the Gangdese arc during the Late Mesozoic, a large amount of continental crust was returned back into the mantle through lateral subduction erosion at the same time. This study provides important insights into long‐term material recycling on Earth.
Plain Language Summary
Arc magmatism plays a significant role in the formation of new crust, tectonic erosion has also been suggested to represent a major process associated with the destruction of continental crust. Crust generation and destruction triggered by subduction sustain the volume of the continental crust in some modern arcs, but subduction erosion is difficult to identify in fossil convergent systems and whether or not this balancing act is a common process over long geological period has been unclear. Here we report geochronologic‐geochemical‐isotopic data on Mesozoic igneous rocks in the central‐eastern Gangdese arc, which is widely considered to have been a very important area for Phanerozoic crustal growth. We consider magmatism along with integrated tectonic and sedimentological evidence to constrain the subduction erosion history of the Gangdese arc. We propose that the southern part of Eurasia was a typical erosive plate margin during the Late Mesozoic comparable to modern Andean arc. Although there was significant vertical growth of juvenile crust throughout the Gangdese arc during the Late Mesozoic, a large amount of continental crust was returned back into the mantle through lateral erosion at the same time. This study provides important insights into long‐term material recycling and crustal evolution on Earth.
Key Points
The Late Mesozoic Gangdese arc suffered extensive tectonic erosion triggered by the subduction of Neotethyan oceanic slab
Significant vertical growth and lateral erosion of continental crust occurred approximately contemporaneously in the Late Mesozoic Gangdese
Crustal generation and destruction triggered by subduction are common and long‐term processes that sustain the volume of continental crust
Sialon ceramics were prepared by the nitridation of Si, Al and Al
2
O
3
powders with the transition metals (Fe, Co, Ni) catalysts. The phase composition, microstructure and mechanical properties of ...specimens were studied. Compared with the catalyst-free specimen, the addition of Fe, Co and Ni greatly promoted the nitridation process of Sialon ceramics and improved the weight gain rate and mechanical properties of specimens. With the increased content of catalysts, the apparent porosity of the products decreased first and then increased, contrary to flexural strength and compressive strength. The specimen with 2.5 wt% Fe had the highest flexural strength 145.8 MPa, and it exhibited the highest compressive strength of 594.6 MPa when Co content was 2.5 wt%, whereas they were 71.9 and 78.7 MPa, respectively, when without catalyst.
Graphic abstract
Infectious diseases, including COVID-19, are crucial public health issues and may lead to considerable fear among the general public and stigmatization of, and discrimination against, specific ...populations. This meta-analysis aimed to estimate the pooled prevalence of stigma in infectious disease epidemics. We systematically searched PubMed, PsycINFO, Embase, MEDLINE, Web of Science, and Cochrane databases since inception to June 08, 2021, and reported the prevalence of stigma towards people with infectious diseases including SARS, H1N1, MERS, Zika, Ebola, and COVID-19. A total of 50 eligible articles were included that contributed 51 estimates of prevalence in 92722 participants. The overall pooled prevalence of stigma across all populations was 34% 95% CI: 28-40%, including enacted stigma (36% 95% CI: 28-44%) and perceived stigma (31% 95% CI: 22-40%). The prevalence of stigma in patients, community population, and health care workers, was 38% 95% CI: 12- 65%, 36% 95% CI: 28-45%, and 30% 95% CI: 20-40%, respectively. The prevalence of stigma in participants from low- and middle-income countries was 37% 95% CI: 29-45%, which is higher than that from high-income countries (27% 95% CI: 18-36%) though this difference was not statistically significant. A similar trend of prevalence of stigma was also observed in individuals with lower education (47% 95% CI: 23-71%) compared to higher education level (33% 95% CI: 23-4%). These findings indicate that stigma is a significant public health concern, and effective and comprehensive interventions are needed to counteract the damaging effects of the infodemics during infectious disease epidemics, including COVID-19, and reduce infectious disease-related stigma.
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