Sensing platform for the highly sensitive detection of catechol based on composite coupling with conductive Ni3(HITP)2 and nanosilvers.

Catechol, which has a high toxicity and low degradability, poses significant risks to both human health and the environment. Tracking of catechol residues is essential to protect human health and to assess the safety of the environment. We constructed sensing platforms to detect catechol based on the conductive metal-organic frameworks [Ni3(HITP)2] and their nanosilver composites. The reduction process of catechol at the Ni3(HITP)2/AgNP electrode is chemically irreversible as a result of the difference in compatibility of the oxidation stability and conductivity between the Ni3(HITP)2/AgNS and Ni3(HITP)2/AgNP electrodes. The electrochemical results show that the Ni3(HITP)2/AgNS electrode presents a lower detection limit of 0.053 µM and better sensitivity, reproducibility and repeatability than the Ni3(HITP)2/AgNP electrode. The kinetic mechanism of the catechol electrooxidation at the surface of the electrode is controlled by diffusion through a 2H+/2e- process. The transfer coefficient is the key factor used to illustrate this process. During the electrochemical conversion of phenol to ketone, more than half of ΔG is used to change the activation energy. We also studied the stability, anti-interference and reproducibility of these electrode systems.

Delivery of mRNA Vaccine with 1, 2-Diesters-Derived Lipids Elicits Fast Liver Clearance for Safe and Effective Cancer Immunotherapy.

Messenger RNA (mRNA) vaccine is explored as a promising strategy for cancer immunotherapy, but the side effects, especially the liver-related damage caused by LNP, raise concerns about its safety. In this study, a novel library of 248 ionizable lipids comprising 1,2-diesters is designed via a two-step process involving the epoxide ring-opening reaction with carboxyl group-containing alkyl chains followed by an esterification reaction with the tertiary amines. Owing to the special chemical structure of 1,2-diesters, the top-performing lipids and formulations exhibit a faster clearance rate in the liver, contributing to increased stability and higher safety compared with DLin-MC3-DMA. Moreover, the LNP shows superior intramuscular mRNA delivery and elicits robust antigen-specific immune activation. The vaccinations delivered by the LNP system suppress tumor growth and prolong survival in both model human papillomavirus E7 and ovalbumin antigen-expressing tumor models. Finally, the structure of lipids which enhances the protein expression in the spleen and draining lymph nodes compared with ALC-0315 lipid in Comirnaty is further optimized. In conclusion, the 1, 2-diester-derived lipids exhibit rapid liver clearance and effective anticancer efficiency to different types of antigens-expressing tumor models, which may be a safe and universal platform for mRNA vaccines.

Designed fabrication of MoS2 hollow structures with different geometries and the comparative investigation toward capacitive properties.

Hollow MoS2 cubes and spheres were synthesized by a one-step hydrothermal method with the hard template method. The structure and morphology were characterized, and their electrochemical properties were studied. It is concluded that the specific capacitance of the hollow MoS2 cubes (335.7 F g-1) is higher than that of the hollow MoS2 spheres (256.1 F g-1). The symmetrical supercapacitors were assembled, and the results indicate that the specific capacitance of the device composed of hollow MoS2 spheres (32.9 F g-1) is slightly lower than that of the hollow MoS2 cube (37.4 F g-1) device. Furthermore, the symmetrical supercapacitor (MoS2-cube//MoS2-cube) provides a maximum energy density of 4.93 W h kg-1, which is greater than that of the symmetrical capacitor (MoS2-sphere//MoS2-sphere, 3.65 W h kg-1). This may indicate that hollow molybdenum disulfide cubes with substructures have more efficient charge transfer capabilities and better capacitance characteristics than hollow spheres. After 8000 cycles, the coulombic efficiency of the two symmetrical capacitors is close to 100%. The capacity retention of the MoS2 sphere device (95.2%) is slightly higher than that of the MoS2 cube device (90.1%). These results show that the pore structure, specific surface, and active site of MoS2 with different hollow structures have a greater impact on its electrochemical properties.

Predicting the current and future distributions of Pennisetum alopecuroides (L.) in China under climate change based on the MaxEnt model.

Pennisetum alopecuroides (L.), one of the important exotic plants, gives great economic value to animal husbandry in China. In order to study the distribution of Pennisetum alopecuroides (L.) in China and its response to climate change, based on the distribution records of Pennisetum alopecuroides (L.), our study used the Maximum Entropy (MaxEnt) model and geographic information system (GIS) methods, combined with environmental factors such as climate and terrain, to predict the potential distribution areas suitable for Pennisetum alopecuroides (L.) under current and future climate scenarios. The results showed that annual precipitation was the most important factor affecting the distribution of Pennisetum alopecuroides (L.). In current climate scenario, the total area of suitable for Pennisetum alopecuroides (L.) growth was about 576.5 km2, accounting for about 60.5% of the total land area of China. Among all the suitable areas, the area of low, middle and high fitness areas accounted for 5.69%, 20.55% and 33.81% of the total area respectively. In future climate scenarios (RCP4.5), the suitable area of Pennisetum alopecuroides (L.) would decrease with climate change, showing a clear trend of northward expansion in China. A concentrated and contiguous distribution region for Pennisetum alopecuroides (L.) would appear in northeast China. The model was tested by the receiver operating characteristic curve (ROC), and the average area under the curve of ROC of the training set was 0.985, which was reliable. This work provided an important reference and theoretical basis for the efficient utilization and plant regionalization of Pennisetum alopecuroides (L.) in future.

Intelligent fault diagnosis of helical gearboxes with compressive sensing based non-contact measurements.

Helical gearboxes play a critical role in power transmission of industrial applications. They are vulnerable to various faults due to long-term and heavy-duty operating conditions. To improve the safety and reliability of helical gearboxes, it is necessary to monitor their health conditions and diagnose various types of faults. The conventional measurements for gearbox fault diagnosis mainly include lubricant analysis, vibration, airborne acoustics, thermal images, electrical signals, etc. However, a single domain measurement may lead to unreliable fault diagnosis and the contact installation of transducers is not always accessible, especially in harsh and dangerous environments. In this article, a Compressive Sensing (CS)-based Dual-Channel Convolutional Neural Network (CNN) method was proposed to accurately and intelligently diagnose common gearbox faults based on two complementary non-contact measurements (thermal images and acoustic signals) from a mobile phone. The raw acoustic signals were analysed by the Modulation Signal Bispectrum (MSB) to highlight the coupled modulation components relating to gear faults and suppress the irrelevant components and random noise, which generates a series of two-dimensional matrices as sparse MSB magnitude images. Then, CS was used to reduce the image redundancy but retain key information owing to the high sparsity of thermal images and acoustic MSB images, which significantly accelerates the CNN training speed. The experimental results convincingly demonstrate that the proposed CS-based Dual-Channel CNN method significantly improves the diagnostic accuracy (99.39% on average) of industrial helical gearbox faults compared to the single-channel ones.

[Corrigendum] Overexpression of HES6 has prognostic value and promotes metastasis via the Wnt/ß-catenin signaling pathway in colorectal cancer.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that Fig. 2 on p. 1266 and Fig. 5 on p. 1269 contained some apparent errors in terms of the assembly of the various data panels. Specifically, Fig. 2D appeared to contain a pair of overlapping images, and Figs. 5D and 8A also appeared to include overlapping images. However, the authors were able to consult their original data, and assess where the errors had been made during the compilation of these figures. The corrected versions of Figs. 2 (showing the correct data for the '5T' panel in Fig. 2D) and 5 (showing alternative data) are shown on the subsequent pages. The authors regret the errors that were made during the preparation of the published figures, and confirm that these errors did not grossly affect the conclusions reported in the study. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish a Corrigendum, and all the authors agree to this Corrigendum. Furthermore, they apologize to the readership for any inconvenience caused. [the original article was published in Oncology Reports 40: 1261­1274, 2018; DOI: 10.3892/or.2018.6539].

Enhancement of Resistive Switching Performance in Hafnium Oxide (HfO2) Devices via Sol-Gel Method Stacking Tri-Layer HfO2/Al-ZnO/HfO2 Structures.

Resistive random-access memory (RRAM) is a promising candidate for next-generation non-volatile memory. However, due to the random formation and rupture of conductive filaments, RRMS still has disadvantages, such as small storage windows and poor stability. Therefore, the performance of RRAM can be improved by optimizing the formation and rupture of conductive filaments. In this study, a hafnium oxide-/aluminum-doped zinc oxide/hafnium oxide (HfO2/Al-ZnO/HfO2) tri-layer structure device was prepared using the sol-gel method. The oxygen-rich vacancy Al-ZnO layer was inserted into the HfO2 layers. The device had excellent RS properties, such as an excellent switch ratio of 104, retention of 104 s, and multi-level storage capability of six resistance states (one low-resistance state and five high-resistance states) and four resistance states (three low-resistance states and one high-resistance state) which were obtained by controlling stop voltage and compliance current, respectively. Mechanism analysis revealed that the device is dominated by ohmic conduction and space-charge-limited current (SCLC). We believe that the oxygen-rich vacancy concentration of the Al-ZnO insertion layer can improve the formation and rupture behaviors of conductive filaments, thereby enhancing the resistive switching (RS) performance of the device.

mRNA produced by VSW-3 RNAP has high-level translation efficiency with low inflammatory stimulation.

In vitro preparation of mRNA is a key step for mRNA therapeutics. The widely used T7 RNA polymerase (RNAP) was shown to have many by-products during in vitro transcription (IVT) process, among which double-stranded RNA (dsRNA) is the major by-product to activate the intracellular immune response. Here, we describe the use of a new VSW-3 RNAP that reduced dsRNA production during IVT and the resulting mRNA exhibited low inflammatory stimulation in cells. Compared to T7 RNAP transcripts, these mRNA exhibited superior protein expression levels, with an average of 14-fold increase in Hela cells and 5-fold increase in mice. In addition, we found that VSW-3 RNAP did not require modified nucleotides to improve protein production of IVT products. Our data suggest that VSW-3 RNAP could be a useful tool for mRNA therapeutics.

The key regulator LcERF056 enhances salt tolerance by modulating reactive oxygen species-related genes in Lotus corniculatus.

BACKGROUND: The APETALA2/ethylene response factor (AP2/ERF) family are important regulatory factors involved in plants' response to environmental stimuli. However, their roles in salt tolerance in Lotus corniculatus remain unclear. RESULTS: Here, the key salt-responsive transcription factor LcERF056 was cloned and characterised. LcERF056 belonging to the B3-1 (IX) subfamily of ERFs was considerably upregulated by salt treatment. LcERF056-fused GFP was exclusively localised to nuclei. Furthermore, LcERF056- overexpression (OE) transgenic Arabidopsis and L. corniculatus lines exhibited significantly high tolerance to salt treatment compared with wild-type (WT) or RNA interference expression (RNAi) transgenic lines at the phenotypic and physiological levels. Transcriptome analysis of OE, RNAi, and WT lines showed that LcERF056 regulated the downstream genes involved in several metabolic pathways. Chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR) and yeast one-hybrid (Y1H) assay demonstrated that LcERF056 could bind to cis-element GCC box or DRE of reactive oxygen species (ROS)-related genes such as lipid-transfer protein, peroxidase and ribosomal protein. CONCLUSION: Our results suggested that the key regulator LcERF056 plays important roles in salt tolerance in L. corniculatus by modulating ROS-related genes. Therefore, it may be a useful target for engineering salt-tolerant L. corniculatus or other crops.

MYBL2 disrupts the Hippo-YAP pathway and confers castration resistance and metastatic potential in prostate cancer.

Rationale: Resistance to androgen-deprivation therapy (ADT) associated with metastatic progression remains a challenging clinical task in prostate cancer (PCa) treatment. Current targeted therapies for castration-resistant prostate cancer (CRPC) are not durable. The exact molecular mechanisms mediating resistance to castration therapy that lead to CRPC progression remain obscure. Methods: The expression of MYB proto-oncogene like 2 (MYBL2) was evaluated in PCa samples. The effect of MYBL2 on the response to ADT was determined by in vitro and in vivo experiments. The survival of patients with PCa was analyzed using clinical specimens (n = 132) and data from The Cancer Genome Atlas (n = 450). The mechanistic model of MYBL2 in regulating gene expression was further detected by subcellular fractionation, western blotting, quantitative real-time PCR, chromatin immunoprecipitation, and luciferase reporter assays. Results: MYBL2 expression was significantly upregulated in CRPC tissues and cell lines. Overexpression of MYBL2 could facilitate castration-resistant growth and metastatic capacity in androgen-dependent PCa cells by promoting YAP1 transcriptional activity via modulating the activity of the Rho GTPases RhoA and LATS1 kinase. Importantly, targeting MYBL2, or treatment with either the YAP/TAZ inhibitor Verteporfin or the RhoA inhibitor Simvastatin, reversed the resistance to ADT and blocked bone metastasis in CRPC cells. Finally, high MYBL2 levels were positively associated with TNM stage, total PSA level, and Gleason score and predicted a higher risk of metastatic relapse and poor prognosis in patients with PCa. Conclusions: Our results reveal a novel molecular mechanism conferring resistance to ADT and provide a strong rationale for potential therapeutic strategies against CRPC.

Deletion of Wild-type p53 Facilitates Bone Metastatic Function by Blocking the AIP4 Mediated Ligand-Induced Degradation of CXCR4.

Background: Management of patients with prostate cancer and bone metastatic disease remains a major clinical challenge. Loss or mutation of p53 has been identified to be involved in the tumor progression and metastasis. Nevertheless, direct evidence of a specific role for wild-type p53 (wt-p53) in bone metastasis and the mechanism by which this function is mediated in prostate cancer remain obscure. Methods: The expression and protein levels of wt-53, AIP4, and CXCR4 in prostate cancer cells and clinical specimens were assessed by real-time PCR, immunohistochemistry and western blot analysis. The role of wt-p53 in suppressing aggressive and metastatic tumor phenotypes was assessed using in vitro transwell chemotaxis, wound healing, and competitive colocalization assays. Furthermore, whether p53 deletion facilitates prostate cancer bone-metastatic capacity was explored using an in vivo bone-metastatic model. The mechanistic model of wt-p53 in regulating gene expression was further explored by a luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay. Results: Our findings revealed that wt-p53 suppressed the prostate cancer cell migration rate, chemotaxis and attachment toward the osteoblasts in vitro. The bone-metastatic model showed that deletion of wt-p53 remarkably increased prostate cancer bone-metastatic capacity in vivo. Mechanistically, wt-p53 could induce the ligand-induced degradation of the chemokine receptor CXCR4 by transcriptionally upregulating the expression of ubiquitin ligase AIP4. Treatment with the CXCR4 inhibitor AMD3100 or transduction of the AIP4 plasmid abrogated the pro-bone metastasis effects of TP53 deletion. Conclusion: Wt-p53 suppresses the metastasis of prostate cancer cells to bones by regulating the CXCR4/CXCL12 activity in the tumor cells/bone marrow microenvironment interactions. Our findings suggest that targeting the wt-p53/AIP4/CXCR4 axis might be a promising therapeutic strategy to manage prostate cancer bone metastasis.

Comparing two sample pooling strategies for SARS-CoV-2 RNA detection for efficient screening of COVID-19.

The emerging pandemic of coronavirus disease 2019 (COVID-19) has affected over 200 countries and resulted in a shortage of diagnostic resources globally. Rapid diagnosis of COVID-19 is vital to control the spreading of the disease, which, however, is challenged by limited detection capacity and low detection efficiency in many parts of the world. The pooling test may offer an economical and effective approach to increase the virus testing capacity of medical laboratories without requiring more laboratory resources such as laboratory workers, testing reagents, and equipment. In this study, the sample pools of 6 and 10 were detected by a real-time reverse transcription-polymerase chain reaction assay targeting ORF1ab and N genes of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Each pool consisted of five or nine negative SARS-CoV-2 samples and one positive counterpart with varying viral loads. Two different strategies of sample pooling were investigated and the results were compared comprehensively. One approach was to pool the viral transport medium of the samples in the laboratory, and the other was to pool swab samples during the collection process. For swab pooling strategy, qualitative results of SARS-CoV-2 RNA, specific tests of ORF1ab and N genes, remained stable over the different pool sizes. Together, this study demonstrates that the swab pooling strategy may serve as an effective and economical approach for screening SARS-CoV-2 infections in large populations, especially in countries and regions where medical resources are limited during the pandemic and may thus be potential for clinical laboratory applications.

Molybdenum sulfide-based electrochemical platform for high sensitive detection of taxifolin in Chinese medicine.

MoS2 and nitrogen doped active carbon composite (MoS2/ANC) is fabricated to detect taxifolin and exhibits superior redox current response and decreased redox potential difference. Further investigation reveals that the kinetic process of the redox reaction of taxifolin on MoS2/ANC electrode is controlled by both adsorption and diffusion process. Under the optimum conditions, the redox peak currents linearly relate with the concentration of taxifolin in the range of 1 × 10-9-1 × 10-6 mol L-1, accompanied by the low detection limit (3 × 10-10 mol L-1). Meanwhile, outstanding selectivity, stability and repeatability are also obtained at MoS2/ANC electrode. At last, the proposed method is applied to quantitatively detect taxifolin in fructus polygoni orientalis and satisfactory results have been achieved.

A Novel Fault Detection Method for Rolling Bearings Based on Non-Stationary Vibration Signature Analysis.

To realize the accurate fault detection of rolling element bearings, a novel fault detection method based on non-stationary vibration signal analysis using weighted average ensemble empirical mode decomposition (WAEEMD) and modulation signal bispectrum (MSB) is proposed in this paper. Bispectrum is a third-order statistic, which can not only effectively suppress Gaussian noise, but also help identify phase coupling. However, it cannot effectively decompose the modulation components which are inherent in vibration signals. To alleviate this issue, MSB based on the modulation characteristics of the signals is developed for demodulation and noise reduction. Still, the direct application of MSB has some interfering frequency components when extracting fault features from non-stationary signals. Ensemble empirical mode decomposition (EEMD) is an advanced nonlinear and non-stationary signal processing approach that can decompose the signal into a list of stationary intrinsic mode functions (IMFs). The proposed method takes advantage of WAEEMD and MSB for bearing fault diagnosis based on vibration signature analysis. Firstly, the vibration signal is decomposed into IMFs with a different frequency band using EEMD. Then, the IMFs are reconstructed into a new signal by the weighted average method, called WAEEMD, based on Teager energy kurtosis (TEK). Finally, MSB is applied to decompose the modulated components in the reconstructed signal and extract the fault characteristic frequencies for fault detection. Furthermore, the efficiency and performance of the proposed WAEEMD-MSB approach is demonstrated on the fault diagnosis for a motor bearing outer race fault and a gearbox bearing inner race fault. The experimental results verify that the WAEEMD-MSB has superior performance over conventional MSB and EEMD-MSB in extracting fault features and has precise and effective advantages for rolling element bearing fault detection.

Overexpression of HES6 has prognostic value and promotes metastasis via the Wnt/ß-catenin signaling pathway in colorectal cancer.

HES6 is a member of the hairy-enhancer of the split homolog family, which has been implicated in oncogenesis and cancer progression in a variety of human cancers, including prostate and breast cancer. However, its clinical significance and biological role in colorectal cancer (CRC) remain unclear. In the present study, the expression of HES6 was significantly upregulated in CRC cell lines and CRC tissues at both the mRNA and protein levels. The present study also reported high expression of HES6 in 138/213 (64.8%) paraffin-embedded archived CRC specimens. HES6 expression was significantly correlated with T classification (P<0.001), N classification (P=0.020), and distant metastasis (P<0.001). Patients with higher HES6 expression levels exhibited a reduced overall survival (P<0.001). In addition, a multivariate analysis revealed that the expression of HES6 may be a novel prognostic marker for the survival of patients with CRC. Furthermore, the present study demonstrated that ectopic expression of HES6 enhanced the migration and invasive abilities of CRC cells. These abilities were significantly inhibited upon knockdown of endogenous HES6 expression by specific short hairpin RNAs. Additionally, the present study reported that the effects of HES6 on metastasis may be associated with the activation of the Wnt/ß-catenin signaling pathway. Collectively, the findings of the present study revealed that overexpression of HES6 played a key role in the progression of CRC, leading to a poor prognosis and clinical outcome.

Mg2+ reduces biofilm quantity in Acidithiobacillus ferrooxidans through inhibiting Type IV pili formation.

Bioleaching is a promising process for 350 million tons of Jinchuan low-grade pentlandite. But high concentration of Mg2+ is harmful to bioleaching microorganisms. Interestingly, biofilm formation can improve leaching rate. Thus, it is actually necessary to investigate the effect of Mg2+ stress on Acidithiobacillus ferrooxidans biofilms formation. In this study, we found that 0.1 and 0.5 M Mg2+ stress significantly reduced the total biomass of biofilm in a dose-dependent manner. The observation results of extracellular polymeric substances and bacteria using confocal laser scanning microscopy showed that the biofilm became thinner and looser under Mg2+ stress. Whereas 0.1 and 0.5 M Mg2+ stress had no remarkable effect on the bacterial viability, the attachment rate of Acidithiobacillus ferrooxidans to pentlandite was reduced by Mg2+ stress. Furthermore, sliding motility, twitching motility and the gene expression level of pilV and pilW were inhibited under Mg2+ stress. These results suggested that Mg2+ reduced biofilm formation through inhibiting pilV and pilW gene expression, decreasing Type IV pili formation and then attenuating the ability of attachment, subduing the active expansion of biofilms mediated by twitching motility. This study provided more information about the effect of Mg2+ stress on biofilm formation and may be useful for increasing the leaching rate in low-grade pentlandit.

miR-145 suppresses colorectal cancer cell migration and invasion by targeting an ETS-related gene.

MicroRNA-45 (miR-145) has been demonstrated to be downregulated in various cancer types including colorectal cancer (CRC). However, the function of miR­145 in CRC has not been clearly elucidated. In this study, we examined miR-145 expression by quantitative real­time PCR (qRT­PCR) in CRC cell lines as well as tumors and corresponding normal mucosa, and the results were correlated to the clinicopathological parameters. In addition, using computational algorithms we investigated putative miR­145 targets. The role of miR­145 was further examined in studies in vitro. In our study miR­145 was significantly decreased in CRC tissues and cell lines compared with non­cancerous colorectal mucosa, especially lymph node or distance metastasis cases. Based on computational algorithms, we assumed that ERG was directly modulated by miR­145 in colorectal cancer cells. For the first time, we demonstrated that ERG was highly expressed in CRC tissues compared with normal ones by qRT­PCR. The inverse correlation between the expression of miR­145 and ERG was observed in CRC tissues. Dual­Luciferase assays demonstrated the direct interaction between miR­145 and 3'­UTR of ERG mRNA. Ectopic expression of miR­145 suppressed the proliferation and invasion ability of colorectal cancer cells, while ERG knockdown partially restored the tumor suppressive effect of miR­145. These results suggested that miR­145 might act as a tumor suppressor during the process of CRC malignant transformation by interacting with ERG.

Overexpressed CISD2 has prognostic value in human gastric cancer and promotes gastric cancer cell proliferation and tumorigenesis via AKT signaling pathway.

CDGSH iron sulfur domain 2 (CISD2) is localized in the outer mitochondrial membrane and mediates mitochondrial integrity and lifespan in mammals, but its role in cancer is unknown. In the current study, we reported that CISD2 mRNA and protein expression levels were significantly upregulated in gastric cancer cells compared to normal gastric epithelial cells (P < 0.001). Immunohistochemical analysis of 261 paraffin-embedded archived gastric cancer tissues showed that high CISD2 expression was significantly associated with clinical stage, TNM classifications, venous invasion and lymphatic invasion. Univariate and multivariate analysis indicated that high CISD2 expression was an independent prognostic factor for poorer overall survival in the entire cohort. Overexpressing CISD2 promoted, while silencing CISD2 inhibited, the proliferation of gastric cancer cells. Furthermore, we found that silencing endogenous CISD2 also significantly inhibited the proliferation and tumorigenicity of MGC-803 and SGC-7901 cells not only in vitro but also in vivo in NOD/SCID mice (P < 0.05). Furthermore, we found that CISD2 affected cell proliferation and tumorigenicity of gastric cancer cells through mediating the G1-to-S phase transition. Moreover, we demonstrated that the pro-proliferative effect of CISD2 on gastric cancer cells was associated with downregulation of cyclin-dependent kinase inhibitor p21Cip1 and p27Kip1, and activation of AKT signaling. The findings of this study indicate that CISD2 may promote proliferation and tumorigenicity, potentially representing a novel prognostic marker for overall survival in gastric cancer.

The potential value of miR-1 and miR-374b as biomarkers for colorectal cancer.

The mortality of colorectal cancer (CRC) is growing due to the unsatisfactory specificity and sensitivity of the existing screening methods. Previous studies have focused on the role of miRNAs as CRC biomarkers. However, few studies have examined the miRNA profiles at each stage. The objective of this study was to identify miRNAs that distinguish CRC patients from normal people to prevent the misdiagnosis of patients with certain stages of CRC. We performed miRNA profiling of 1547 human miRNAs by qRT-PCR in CRC patients with stage II and stage III disease. The statistical analyses showed that there were 96 miRNAs that were significantly dysregulated in CRC relative to normal tissues (P<0.05). There were 28 dysregulated miRNAs associated with separate or combined stages II and III disease. There were 25 downregulated miRNAs, including the following: miR-1, -145, -145*, -137, -363, -143, -4770, -490-5p, -9, -144*, -99a, -99b, -23b, -143*, -100, -768-3p, -24-1*, -125a-5p, -30e*, -574-3p, -126, let-7b, miR-1979, -374b, and -140-3p. We found an upregulation of miR-203, 182, and 96. Our results demonstrated that the expression of miR-1 and miR-374b was significantly decreased in each stage and may function as a biomarker of CRC. Furthermore, 20 miRNAs were dysregulated both in stage II disease without lymph node or distant metastasis and in stage II-III tumors but not in stage III tumors. Only miR-4794 was involved exclusively with stage II tumors, and there were 19 miRNAs that were dysregulated only in stage III disease with lymph node metastasis and in stage II-III disease. There were only 6 miRNAs that were uniquely dysregulated in stage III. Our results indicate that miRNA expression may be valuable in the clinic. However, large prospective studies are required to confirm the role of miRNAs. This study provides a new model for analyzing novel CRC biomarkers by considering more clinical factors.