Copy number alterations (CNAs) are crucial for colorectal cancer (CRC) development. In this study, DEAD box polypeptide 27 (DDX27) was identified to be highly amplified in both TCGA CRC (474/615) and ...primary CRC (47/103), which was positively correlated with its mRNA overexpression. High DDX27 mRNA (N = 199) and protein expression (N = 260) predicted poor survival in CRC patients. Ectopic expression of DDX27 increased CRC cells proliferation, migration and invasion, but suppressed apoptosis. Conversely, silencing of DDX27 exerted opposite effects in vitro and significantly inhibited murine xenograft tumor growth and lung metastasis in vivo. Up-regulation of DDX27 enhanced and prolonged TNF-α-mediated NF-κB signaling. Nucleophosmin (NPM1) was identified as a binding partner of DDX27. DDX27 increased nuclear NPM1 and NF-κB-p65 interaction to enhance DNA binding activity of NF-κB. Silencing NPM1 abrogated DDX27-activating NF-κB signaling and its tumor-promoting function. Together, DDX27 is overexpressed and plays a pivotal oncogenic role in CRC.
Abstract
The detection of tumor-derived cell-free DNA in plasma is one of the most promising directions in cancer diagnosis. The major challenge in such an approach is how to identify the tiny amount ...of tumor DNAs out of total cell-free DNAs in blood. Here we propose an ultrasensitive cancer detection method, termed 'CancerDetector', using the DNA methylation profiles of cell-free DNAs. The key of our method is to probabilistically model the joint methylation states of multiple adjacent CpG sites on an individual sequencing read, in order to exploit the pervasive nature of DNA methylation for signal amplification. Therefore, CancerDetector can sensitively identify a trace amount of tumor cfDNAs in plasma, at the level of individual reads. We evaluated CancerDetector on the simulated data, and showed a high concordance of the predicted and true tumor fraction. Testing CancerDetector on real plasma data demonstrated its high sensitivity and specificity in detecting tumor cfDNAs. In addition, the predicted tumor fraction showed great consistency with tumor size and survival outcome. Note that all of those testing were performed on sequencing data at low to medium coverage (1× to 10×). Therefore, CancerDetector holds the great potential to detect cancer early and cost-effectively.
The pandemic novel coronavirus infection, Coronavirus Disease 2019 (COVID-19), has affected at least 190 countries or territories, with 465,915 confirmed cases and 21,031 deaths. In a ...containment-based strategy, rapid, sensitive and specific testing is important in epidemiological control and clinical management. Using 96 SARS-CoV-2 and 104 non-SARS-CoV-2 coronavirus genomes and our in-house program, GolayMetaMiner, four specific regions longer than 50 nucleotides in the SARS-CoV-2 genome were identified. Primers were designed to target the longest and previously untargeted nsp2 region and optimized as a probe-free real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. The new COVID-19-nsp2 assay had a limit of detection (LOD) of 1.8 TCID
/mL and did not amplify other human-pathogenic coronaviruses and respiratory viruses. Assay reproducibility in terms of cycle threshold (Cp) values was satisfactory, with the total imprecision (% CV) values well below 5%. Evaluation of the new assay using 59 clinical specimens from 14 confirmed cases showed 100% concordance with our previously developed COVID-19-RdRp/Hel reference assay. A rapid, sensitive, SARS-CoV-2-specific real-time RT-PCR assay, COVID-19-nsp2, was developed.
Abstract
Background
Coronavirus Disease 2019 (COVID-19) led to pandemic that affected almost all countries in the world. Many countries have implemented border restriction as a public health measure ...to limit local outbreak. However, there is inadequate scientific data to support such a practice, especially in the presence of an established local transmission of the disease.
Objective
To apply a metapopulation Susceptible-Exposed-Infectious-Recovered (SEIR) model with inspected migration to investigate the effect of border restriction as a public health measure to limit outbreak of coronavirus disease 2019.
Methods
We apply a modified metapopulation SEIR model with inspected migration with simulating population migration, and incorporating parameters such as efficiency of custom inspection in blocking infected travelers in the model. The population sizes were retrieved from government reports, while the number of COVID-19 patients were retrieved from Hong Kong Department of Health and China Centre for Disease Control (CDC) data. The
R
0
was obtained from previous clinical studies.
Results
Complete border closure can help to reduce the cumulative COVID-19 case number and mortality in Hong Kong by 13.99% and 13.98% respectively. To prevent full occupancy of isolation facilities in Hong Kong; effective public health measures to reduce local
R
0
to below 1.6 was necessary, apart from having complete border closure.
Conclusions
Early complete travel restriction is effective in reducing cumulative cases and mortality. However, additional anti-COVID-19 measures to reduce local
R
0
to below 1.6 are necessary to prevent COVID-19 cases from overwhelming hospital isolation facilities.
•Nitzschia laevis was a promising resource to develop fucoxanthinol and fucoxanthin production.•A simple two-step method was mediated with SPE and TLC techniques.•This exploited approach could ...effectively purified fucoxanthinol and fucoxanthin.•The purities of the two purified compounds were over 95%.
In this study, the microalga Nitzschia laevis (N. laevis) can accumulate a marine carotenoid fucoxanthinol. In particular, fucoxanthinol was firstly isolated from microalgae, accompanied by its derivative fucoxanthin. The identification and quantification of fucoxanthinol and fucoxanthin were determined by ultra-performance liquid chromatography coupled to photodiode array detector-quadrupole/travelling-wave ion mobility mass spectrometry/time-of-flight mass spectrometry (UPLC-PDA-TWIMS-QTOF-MS). Furthermore, a cost-effective approach mediated with solid-phase extraction (SPE) and thin-layer chromatography (TLC) technique was used to isolate and purify fucoxanthinol and fucoxanthin from the extracts of N. laevis. This two-step method can obtain 98% fucoxanthinol and 95% fucoxanthin, with the recovery efficiencies of around 85% for fucoxanthinol and 70% for fucoxanthin, respectively. Moreover, 1H and 13C nuclear magnetic resonance (NMR) techniques were adopted to record the purified compounds for supporting the above results. In all, the developed method has a promising potential to purify fucoxanthinol and fucoxanthin of microalgae for food and pharmaceutical applications.
In order to find out new sources of safe and inexpensive antioxidants, the antioxidant capacities of 45 selected medicinal plants were evaluated using ferric reducing antioxidant power (FRAP) and ...Trolox equivalent antioxidant capacity (TEAC) assays, respectively, and the total phenolic contents of these plants were measured by the Folin–Ciocalteu method. Most of these plants were analyzed for the first time for their antioxidant activities. It was found that the plants
Sargentodoxa cuneata Rehd. Et Wils,
Fraxinus rhynchophylla Hance,
Paeonia lactiflora Pall,
Paeonia suffruticosa Andr and
Scutellaria baicalensis Ceorgi possessed the highest antioxidant capacities and thus could be potential rich sources of natural antioxidants. A strong correlation between TEAC values and those obtained from FRAP assay implied that antioxidants in these plants were capable of scavenging free radicals and reducing oxidants. A high correlation between antioxidant capacities and their total phenolic contents indicated that phenolic compounds were a major contributor of antioxidant activity of these plants.
: The pathogenesis of hepatocellular carcinoma (HCC) is a multistep process contributed by the accumulation of molecular alterations. We identified Apelin (APLN) as an outlier gene up-regulated in ...hepatocellular carcinoma (HCC) through RNA-Seq and microarray analysis. We aimed to investigate its function, mechanism of action and clinical implication in HCC. Methods: Gene expression and clinical implication of APLN were assessed in multiple human HCC cohorts. Ectopic expression and silencing of APLN were performed to determine its function. The therapeutic potential of APLN and its downstream pathway was investigated using
and
models.
: APLN overexpression was commonly observed in more than 80% of HCCs and independently predicted poorer survival of patients in three independent HCC cohorts. Apelin up-regulation was mediated by active β-catenin, which binds to the APLN promoter to induce transcription. Ectopic APLN expression in HCC cells promoted cell proliferation, accelerated G1/S progression and inhibited apoptosis, whilst APLN knockdown exerted opposite effects
and inhibited HCC xenograft growth in mice. Mechanistically, APLN activated phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway via APLN receptor, leading to increased expression of phospho-glycogen synthase kinase 3β (p-GSK3β) and cyclin D1. Pharmacological targeting of APLN by ML221 was safe and effective in inhibiting APLN-PI3K/Akt cascade and HCC growth
and
.
: Our findings unraveled an oncogenic role of APLN in HCC, and that targeting of APLN might be a promising for HCC treatment. APLN may serve as an independent prognostic factor for HCC patients.
The antioxidant activities and total phenolic contents of 30 Chinese medicinal plants were evaluated using the ferric reducing antioxidant power assay and the Folin–Ciocalteu method, respectively. ...The Chinese medicinal plants were extracted by the traditional method, boiling in water and also in 80% methanol. A significant and linear correlation coefficient between the antioxidant activity and the total phenolic content was found in both aqueous (
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2
=
0.7917) and methanol (
R
2
=
0.7584) extracts. Phenolic compounds are thus a major contributor of antioxidant activity. Comparing the extraction efficiency of the two methods, the boiling water method extracted phenolic compounds more efficiently, and antioxidant activity of the extract was higher. It was found that the Chinese medicinal plants
Rhodiola sacra Fu, the stem of
Polygonum multiflorum Thunb. and the root of
P. multiflorum Thunb. possessed the highest antioxidant activities and thus could be potential rich sources of natural antioxidants.
Acute myeloid leukemia (AML) with TP53 mutation is one of the most lethal cancers and portends an extremely poor prognosis. Based on in silico analyses of druggable genes and differential gene ...expression in TP53-mutated AML, we identified pololike kinase 4 (PLK4) as a novel therapeutic target and examined its expression, regulation, pathogenetic mechanisms, and therapeutic potential in TP53-mutated AML. PLK4 expression was suppressed by activated p53 signaling in TP53 wild-type AML and was increased in TP53-mutated AML cell lines and primary samples. Short-term PLK4 inhibition induced DNA damage and apoptosis in TP53 wild-type AML. Prolonged PLK4 inhibition suppressed the growth of TP53-mutated AML and was associated with DNA damage, apoptosis, senescence, polyploidy, and defective cytokinesis. A hitherto undescribed PLK4/PRMT5/EZH2/H3K27me3 axis was demonstrated in both TP53 wild-type and mutated AML, resulting in histone modification through PLK4-induced PRMT5 phosphorylation. In TP53-mutated AML, combined effects of histone modification and polyploidy activated the cGAS-STING pathway, leading to secretion of cytokines and chemokines and activation of macrophages and T cells upon coculture with AML cells. In vivo, PLK4 inhibition also induced cytokine and chemokine expression in mouse recipients, and its combination with anti-CD47 antibody, which inhibited the "don't-eat-me" signal in macrophages, synergistically reduced leukemic burden and prolonged animal survival. The study shed important light on the pathogenetic role of PLK4 and might lead to novel therapeutic strategies in TP53-mutated AML.
A photorefreshable and photoenhanced electrochemical sensing platform for bisphenol A (BPA) detection based on Au nanoparticles (NPs) decorated carbon doped TiO2 nanotube arrays (TiO2/Au NTAs) is ...described. The TiO2/Au NTAs were prepared by quick annealing of anodized nanotubes in argon, followed by controllable electrodeposition of Au NPs. The decoration of Au NPs not only improved photoelectrochemical behavior but also enhanced electrocatalytic activities of the resulted hybrid NTAs. Meanwhile, the high photocatalytic activity of the NTAs allowed the electrode to be readily renewed without damaging the microstructures and surface states after a short UV treatment. The electrochemical detection of BPA on TiO2/Au NTAs electrode was significantly improved under UV irradiation as the electrode could provide fresh reaction surface continuously and the further increased photocurrent resulting from the improved separation efficiency of the photogenerated electron−hole pairs derived from the consumption of holes by BPA. The results showed that the refreshable TiO2/Au NTAs electrode is a promising sensor for long-term BPA monitoring with the detection limit (S/N = 3) of 6.2 nM and the sensitivity of 2.8 μA·μM–1·cm–2.
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