Wenshuai Li

Photoluminescence from SiOx thin films: effects of film thickness and annealing temperature

Photoluminescence (PL) from SiOx (0<x<2) thin films, prepared by evaporation of SiO powder onto the Si(100) substrate followed by thermal annealing, was investigated for various film thickness and annealing temperatures. For the film thickness ranging from 120 to 700 nm and annealing at 1100 °C for 30 min in nitrogen, the Si nanocrystals (nc-Si) embedded in SiO2 matrix were formed due to the phase separation process, and the PL of nc-Si exhibited a continuous red-shift with increasing film thickness in an exponential decay manner. This thickness dependence was explained by a model modified from that of Zacharias and Streitenberger (2000 Phys. Rev. B 62 8391) regarding the nucleation barrier for Si clusters versus their distances away from the substrate. Further, for the film thickness of 270 nm and annealing temperature ranging from 700 to 1100 °C, it was found that a green/yellow PL structure developed at elevated annealing temperatures, which reached the maximum in intensity at 900 °C, and then dropped down for higher annealing temperatures. This PL emission was identified as due to the structural defects mainly consisting of oxygen vacancies in SiO2 matrix.

Identification of miR-423 and miR-499 polymorphisms on affecting the risk of hepatocellular carcinoma in a large-scale population.

AIMS MicroRNAs (miRNAs) regulate gene expression and act as tumor suppressors or enhancers in oncogenesis. Single-nucleotide polymorphisms (SNPs) in miRNAs could alter the processing or actions of mature miRNA. So far, the association of miR-423 rs6505162 with cancers has not been explored, while the association of miR-499 rs3746444 was only reported in small-sized samples of different types of populations. METHODS To evaluate the association of miR-499 rs3746444 and miR-423 rs6505162 with hepatocellular carcinoma (HCC), we performed a large-scale case-control study of 984 patients with HCC and 991 cancer-free controls. RESULTS The risk of HCC was significantly higher with miR-499 rs3746444 TC+CC genotypes compared with those with the TT genotype (odds ratio [OR]=1.372, 95% confidence intervals [CI]=1.099-1.713, p=0.005), as was the risk of hepatitis B virus-related HCC (OR=1.437, 95% CI=1.128-1.831, p=0.003). Moreover, subjects with the TC+CC genotypes were more vulnerable to advanced HCC with larger tumor size (χ(2)=13.014, p=0.001) and/or higher total bilirubin (p=0.004), which suggested that a TT genotype or T allele might serve as a protective factor. miR-423 rs6505162 had no effect on the risk of HCC. CONCLUSIONS miR-499 rs3746444 may contribute to the risk and prognosis of HCC, indicating that this SNP could be developed as a biomarker for HCC prediction.

5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers

DNA modifications such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are epigenetic marks known to affect global gene expression in mammals. Given their prevalence in the human genome, close correlation with gene expression and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology, we report here the genome-wide profiling of 5hmC in circulating cell-free DNA (cfDNA) and in genomic DNA (gDNA) of paired tumor and adjacent tissues collected from a cohort of 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver or thyroid cancer and normal tissues from 90 healthy individuals. 5hmC was mainly distributed in transcriptionally active regions coincident with open chromatin and permissive histone modifications. Robust cancer-associated 5hmC signatures were identified in cfDNA that were characteristic for specific cancer types. 5hmC-based biomarkers of circulating cfDNA were highly predictive of colorectal and gastric cancers and were superior to conventional biomarkers and comparable to 5hmC biomarkers from tissue biopsies. Thus, this new strategy could lead to the development of effective, minimally invasive methods for diagnosis and prognosis of cancer from the analyses of blood samples.

Association between a Variant in MicroRNA-646 and the Susceptibility to Hepatocellular Carcinoma in a Large-Scale Population

Background. Single-nucleotide polymorphisms in microRNAs play important roles in oncogenesis and cancer development. Objective. We aim to explore whether miR-646 rs6513497 is associated with the risk of hepatocellular carcinoma. Methods. Total 997 HCC patients and 993 cancer-free controls were enrolled in this study. Genotyping was performed using MassARRAY method. Results. Compared with the T allele of rs6513497, the G allele was associated with a significantly decreased risk of HCC (OR = 0.788, 95% CI = 0.631–0.985, P = 0.037); moreover, a more protective effect of the G allele was shown in males (OR = 0.695, 95% CI = 0.539–0.897, P = 0.005 in HCC and OR = 0.739, 95% CI = 0.562–0.972, P = 0.030 in HBV-related HCC), basically in a dominant manner (HCC: OR = 0.681, 95% CI = 0.162–0.896, P = 0.006; HBV-related HCC: OR = 0.715, 95% CI = 0.532–0.962, P = 0.027). Conclusions. Our findings support the view that the miR-646 SNP rs6513497 may contribute to the susceptibility of HCC.

The gamma-glutamyl transpeptidase-to-platelet ratio predicts liver fibrosis and cirrhosis in HBeAg-positive chronic HBV infection patients with high HBV DNA and normal or mildly elevated alanine transaminase levels in China.

The gamma‐glutamyl transpeptidase‐to‐platelet ratio (GPR) is a new serum diagnostic model, which is reported to be more accurate than aspartate transaminase‐to‐platelet ratio index (APRI) and fibrosis index based on the four factors (Fib‐4) for the diagnosis of significant fibrosis and cirrhosis in chronic HBV infection (CHBVI) patients in West Africa. To evaluate the performance of the GPR model for the diagnosis of liver fibrosis and cirrhosis in HBeAg‐positive CHBVI patients with high HBV DNA (≥5 log10 copies/mL) and normal or mildly elevated alanine transaminase (ALT) (≤2 times upper limit of normal (ULN)) in China. A total of 1521 consecutive CHBVI patients who underwent liver biopsies and routine laboratory tests were retrospectively screened. Of these patients, 401 treatment naïve HBeAg‐positive patients with HBV DNA≥5 log10 copies/mL and ALT≤2 ULN were included. The METAVIR scoring system was adopted as the pathological diagnosis standard of liver fibrosis. Using liver histology as a gold standard, the performances of GPR, APRI, and Fib‐4 for the diagnosis of liver fibrosis and cirrhosis were evaluated and compared by receiver operating characteristic (ROC) curves and the area under the ROC curves (AUROCs). Of 401 patients, 121 (30.2%), 49 (12.2%) and 17 (4.2%) were classified as having significant fibrosis (≥F2), severe fibrosis (≥F3) and cirrhosis (=F4), respectively. After estimating the AUROC to predict significant fibrosis, the performance of GPR (AUROC=0.66, 95% CI 0.60–0.72) was higher than APRI (AUROC=0.58, 95% CI 0.52–0.64, P=.002) and Fib‐4 scores (AUROC=0.54, 95% CI 0.47–0.60, P<.001). After estimating the AUROC to predict severe fibrosis, the performance of GPR (AUROC=0.71, 95% CI 0.63–0.80) was also higher than APRI (AUROC=0.65, 95% CI 0.56–0.73, P=.003) and Fib‐4 scores (AUROC=0.67, 95% CI 0.58–0.75, P=.001). After estimating the AUROC to predict cirrhosis, the performance of GPR (AUROC=0.73, 95% CI 0.56–0.88) was higher than APRI (AUROC=0.69, 95% CI 0.54–0.83, P=.041) and Fib‐4 scores (AUROC=0.69, 95% CI 0.55–0.82, P=.012) too. The GPR is a new serum model for the diagnosis of liver fibrosis and cirrhosis and shows obvious advantages in Chinese HBeAg‐positive patients with HBV DNA≥5 log10 copies/mL and ALT≤2 ULN compared with APRI and Fib‐4, thus warranting its widespread use for this specific population.

A single nucleotide variant in microRNA-1269a promotes the occurrence and process of hepatocellular carcinoma by targeting to oncogenes SPATS2L and LRP6.

Hepatocellular carcinoma (HCC) is one of the malignant and lethal cancers. Single nucleotide polymorphisms (SNPs) in microRNAs(miRNAs) can affect the expression and target identification of miRNAs and lead to the formation of malignant tumors. However, little is known about whether microRNA-1269a (miR-1269a) SNPs affect the susceptibility and progression of HCC or their specific mechanism. The association between microRNA-1269a rs73239138 and the susceptibility to HCC was verified by MassARRAY assay in a large case-control sample. The effect of miR-1269a and the variant on the proliferation and apoptosis of HCC cells was examined by flow cytometry (FCM), CCK8 assay and Western blot. The target of miR-1269a was identified by bioinformatics analysis and qRT-PCR and its role on cell proliferative capacity was examined by CCK8 assay. The expression level of miR-1269a was analyzed by qRT-PCR in HCC cells transfected with wild or variant type pre-miR-1269a plasmid.MiR-1269a produced a tumor suppressor effect by inhibiting cell proliferation and inducing apoptosis of human HCC cells, possibly via inhibiting the expression of its target genes SPATS2L and LRP6, which were tumor promoters. While, rs73239138 (G>A) in miR-1269a reduced the anticancer effect of miR-1269a possibly by attenuating its total amount in HCC cells or its target recognition, reduce its inhibition on target genes and promoted the susceptibility to HCC. Our findings for the first time proved that miR-1269a SNP plays a role in the occurrence and process of HCC and the relevant mechanism, in accompany with the discovery of the novel target genes of miR-1269a.

Serum microRNA panel excavated by machine learning as a potential biomarker for the detection of gastric cancer

Early detection of gastric cancer (GC) is crucial to improve the therapeutic effect and prolong the survival of patients. MicroRNAs (miRNAs) are a group of small non-protein-coding RNAs that function as repressors of diverse genes. We aimed to identify a microRNA panel in the serum of patients to predict GC non-invasively with high accuracy and sensitivity. Using six types of classifiers, we selected three markers (miR‑21-5p, miR-22-3p and miR-29c-3p) from a published miRNA profiling study (GSE23739) which was treated as a training set. The values of the area under the receiver operating characteristic (ROC) curves (AUCs) were 0.9437, 0.9456 and 0.9563 in the three classifiers [Compound covariate classifier, Diagonal linear discriminant analysis (DLDA) classifier and Support vector machine classifier], respectively. Then the panel was validated further in another two miRNA profiles in GEO (Gene Expression Omnibus) databases (GSE26595, GSE28700) with high AUC values as well. Next, we found that the serum levels of miR-21 were significantly higher in GC patients than levels in healthy controls by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for confirmation, which was opposite to the serum levels of miR-22 and miR-29c (all P<0.0001). Finally, using bioinformatic tools, their biological mechanisms were elucidated by their predicted targets: Sp1 (miR-21) and PTEN (miR-22 and miR-29c). This miRNA panel is a non‑invasive and potential biomarker for GC.

MicroRNA-212 activates hepatic stellate cells and promotes liver fibrosis via targeting SMAD7

There has been an increasing number of researches about microRNAs (miRNAs) in the progression of liver fibrosis from the point of their comprehensive functions in regulating the activation of hepatic stellate cells (HSCs). Among them, it has been reported that miR-212 is up-regulated in activated rat primary HSCs. However, its mechanism has not been determined yet. Here, we confirmed that the level of miR-212-3p was up-regulated in livers of carbon tetrachloride (CCl4)-treated mice compared with the normal control, which is a classical model of chronically damaged fibrotic liver. In vitro, we demonstrated that TGF-β, a master fibrogenic cytokine, could induce the level of miR-212. In turn, overexpression of miR-212 could induce the activation marker of HSC including α-smooth muscle actin (α-SMA) and collagens by activating TGF-β signaling pathway. Furthermore, SMAD7, a dominant suppressor of TGF-β pathway, was identified as a direct target of miR-212-3p. Our results indicate that miR-212-3p facilitates the activation of HSCs and TGF-β pathway by targeting SMAD7, highlighting that it can be served as a novel biomarker or therapeutic target for liver fibrosis.

DNA 5-Hydroxymethylcytosines from Cell-free Circulating DNA as Diagnostic Biomarkers for Human Cancers

DNA modifications such as 5-methylcytosines (5mC) and 5-hydroxymethylcytosines (5hmC) are epigenetic marks known to affect global gene expression in mammals(1, 2). Given their prevalence in the human genome, close correlation with gene expression, and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology(3), we report here genome-wide 5hmC profiling in circulating cell-free DNA (cfDNA) and in genomic DNA of paired tumor/adjacent tissues collected from a cohort of 90 healthy individuals and 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver, or thyroid cancer. 5hmC was mainly distributed in transcriptionally active regions coincident with open chromatin and permissive histone modifications. Robust cancer-associated 5hmC signatures in cfDNA were identified with specificity for different cancers. 5hmC-based biomarkers of circulating cfDNA demonstrated highly accurate predictive value for patients with colorectal and gastric cancers versus healthy controls, superior to conventional biomarkers, and comparable to 5hmC biomarkers from tissue biopsies. This new strategy could lead to the development of effective blood-based, minimally-invasive cancer diagnosis and prognosis approaches.

Association between microRNA single nucleotide polymorphisms and the risk of hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma (HCC) has a high morbidity and mortality. Single nucleotide polymorphisms (SNPs) of microRNA (miRNA) may be associated with the susceptibility to develop certain malignant tumors. AIM To study the association between SNPs of miRNA and hepatocellular carcinoma in peripheral blood samples. MATERIAL AND METHODS Three SNPs in miRNA were studied in peripheral blood samples of 498 patients with HCC and 520 controls. RESULTS A significant association was observed between rs13299349 in miRNA3152 and HCC. AA genotype or A allele were significantly associated with increased risk of HCC. A allele was associated with the size and number of tumor foci. There was also a relationship between rs10061133 in miRNA449b and HCC. The G allele was significantly associated with increased risk of HCC compared with A allele. CONCLUSIONS This study links rs13299349 in miRNA3152 and rs10061133 in miRNA449b with the risk of developing HCC.