The poor prognosis of hepatocellular carcinoma (HCC) has been associated with recurrence and metastasis. Recently, we established a pair of HCC cell lines from a primary (H2-P) and its matched ...metastatic (H2-M) HCC tumors. A high density of cDNA microarray with 9184 human cDNA was used to identify the differentially expressed genes between H2-P and H2-M. Comparing with H2-P, eight upregulated and six downregulated genes were detected in H2-M. One interesting finding is the overexpression of Vimentin (VIM), a well-defined intermediate filament, which has been linked to a more aggressive status in various tumors. The correlation of overexpression of VIM and HCC metastasis was studied by immunohistochemistry using a tissue microarray with 200 primary HCCs and 60 pairs of primary and matched metastatic HCC samples. Tissue microarray demonstrated that the overexpression of VIM was significantly associated with HCC metastasis (P<0.01). This finding strongly suggests that the overexpression of VIM may play an important role in the metastasis of HCC.
Expression profiling studies classified breast carcinomas into estrogen receptor (ER)+/luminal, normal breast-like, HER2 overexpressing, and basal-like groups, with the latter two associated with ...poor outcomes. Currently, there exist clinical assays that identify ER+/luminal and HER2-overexpressing tumors, and we sought to develop a clinical assay for breast basal-like tumors.
To identify an immunohistochemical profile for breast basal-like tumors, we collected a series of known basal-like tumors and tested them for protein patterns that are characteristic of this subtype. Next, we examined the significance of these protein patterns using tissue microarrays and evaluated the prognostic significance of these findings.
Using a panel of 21 basal-like tumors, which was determined using gene expression profiles, we saw that this subtype was typically immunohistochemically negative for estrogen receptor and HER2 but positive for basal cytokeratins, HER1, and/or c-KIT. Using breast carcinoma tissue microarrays representing 930 patients with 17.4-year mean follow-up, basal cytokeratin expression was associated with low disease-specific survival. HER1 expression was observed in 54% of cases positive for basal cytokeratins (versus 11% of negative cases) and was associated with poor survival independent of nodal status and size. c-KIT expression was more common in basal-like tumors than in other breast cancers but did not influence prognosis.
A panel of four antibodies (ER, HER1, HER2, and cytokeratin 5/6) can accurately identify basal-like tumors using standard available clinical tools and shows high specificity. These studies show that many basal-like tumors express HER1, which suggests candidate drugs for evaluation in these patients.
In the polycrystalline SnS semiconductor films, the crystallite size and stoichiometry play a central role in dictating their optoelectronic properties. Most strategies to tailoring these parameters ...require long-time deposition methods and post-deposition thermal annealing at high temperature under inert atmosphere or sulfur vapor. Here, we report a different strategy of tuning optoelectronic properties of SnS films by controlling the kinetical parameters in a microwave-hydrothermal solution method at low temperatures (50–60 °C). The interaction between microwave radiation and the highly polar thioacetamide (TA, sulfur source) enhances local temperature in the reaction solution and permits a rapid formation of orthorhombic SnS crystallites on glass substrates. For as-deposited SnS films, a lineal dependence is observed of the film thickness, crystallite size and electrical conductivity on the TA concentration. In addition, the microstrain, Sn/S ratio and optical band gap of the films decrease with the concentration of TA, leading to the optimal values for stoichiometry and optical properties of SnS films. The ability to synthesize highly crystalline SnS thin films at high growth rates and low temperatures opens up possibilities to the fabrication of SnS-based optoelectronic devices on plastic substrates.
Display omitted
•Crystalline SnS thin films are obtained by microwave heating at low temperatures.•Larger concentration of thioacetamide favors crystallinity of SnS thin films.•Crystallinity and stoichiometry of SnS films are improved with higher temperature.•Synthesis parameters influence on lattice parameters and microstrain of SnS films.•Band-gap values of the SnS thin films are tunable by controlling the crystallite size.
A dental appointment commonly prompts fear of a painful experience, yet we have never fully understood how our brains react to the expectation of imminent tooth pain once in a dental chair. In our ...study, 21 patients with hypersensitive teeth were tested using nonpainful and painful stimuli in a clinical setting. Subjects were tested in a dental chair using functional near-infrared spectroscopy to measure cortical activity during a stepwise cold stimulation of a hypersensitive tooth, as well as nonpainful control stimulation on the same tooth. Patients’ sensory-discriminative and emotional-cognitive cortical regions were studied through the transition of a neutral to a painful stimulation. In the putative somatosensory cortex contralateral to the stimulus, 2 well-defined hemodynamic peaks were detected in the homuncular orofacial region: the first peak during the nonpainful phase and a second peak after the pain threshold was reached. Moreover, in the upper-left and lower-right prefrontal cortices, there was a significant active hemodynamic response in only the first phase, before the pain. Subsequently, the same prefrontal cortical areas deactivated after a painful experience had been reached. Our study indicates for the first time that pain perception and expectation elicit different hemodynamic cortical responses in a dental clinical setting.
POU class 2 homeobox 1 (POU2F1), also known as octamer-binding transcription factor-1 (OCT-1), is a ubiquitous transcription factor that plays a key role in the regulation of genes related to ...inflammation and cell cycles. POU2F1 is located on chromosome 1q24, a region with linkage for Type 2 diabetes in Chinese and other populations. We examined the association of POU2F1 genetic variants with Type 2 diabetes in Hong Kong Chinese using two independent cohorts.
We genotyped five haplotype-tagging single nucleotide polymorphisms at POU2F1 in 1378 clinic-based patients with Type 2 diabetes and 601 control subjects, as well as 707 members from 179 families with diabetes.
We found significant associations of rs4657652, rs7532692, rs10918682 and rs3767434 (OR = 1.26-1.59, 0.0003 < P(unadjusted) < 0.035) with Type 2 diabetes in the clinic-based case-control cohorts. Rs3767434 was also associated with Type 2 diabetes (OR = 1.55, P(unadjusted) = 0.013) in the family-based cohort. Meta-analysis revealed similar associations. In addition, the risk G allele of rs10918682 showed increased usage of insulin treatment during a mean follow-up period of 7 years hazard ratio = 1.50 (1.05-2.14), P = 0.025.
Using separate cohorts, we observed consistent results showing the contribution of multiple variants at POU2F1 to the risk of Type 2 diabetes.
We investigate the impact of microwave excited spin excitations on the dc charge transport in a ferromagnetic (FM) grating. We observe both resonant and nonresonant microwave photoresistance, which ...are caused, respectively, by spin and charge dissipations of the microwave power into the FM. A macroscopic model based on Maxwell and Landau-Lifschitz equations reveals the mixing of spin and charge dissipations, which shows that the ferromagnetic anti-resonance is shifted when the conductivity is anisotropic. We find that the microwave photoconductivity provides a powerful new tool to study the interplay between photonic, spintronic, and charge effects in FM microstructures.
Type 2 diabetes (T2D) is thought to arise from the complex interplay of both genetic and environmental factors. Since the advent of genome-wide association studies (GWAS), we have seen considerable ...progress in our understanding of the role that genetics and gene-environment interactions play in the development of T2D. Recent work suggests that the adverse effect of several T2D loci may be abolished or at least attenuated by higher physical activity levels or healthy lifestyle, whereas low physical activity and dietary factors characterizing a Western dietary pattern may augment it. However, there still remain inconsistencies warranting further investigation. Lack of statistical power and measurement errors for the environmental factors continue to challenge our efforts for characterizing interactions. Although our recent focus on established T2D loci is reasonable, we may be overlooking many other potential loci not captured by recent T2D GWAS. Agnostic approaches to the discovery of gene and environment interactions may address this possibility, but their application to the field is currently limited and still faces conceptual challenges. Nonetheless, continued investment in gene-environment interaction studies through large collaborative efforts holds promise in furthering our understanding of the interplay between genetic and environmental factors.
We tested the hypothesis that the effects on gene expression of altered DNA methylation by 5-aza-2′-deoxycytidine (5-aza-CdR) and genetic (
DNMT knockout) manipulation of DNA are similar, and ...distinct from Trichostatin A (TSA)-induced chromatin decondensation. Surprisingly, the effects of 5-aza-CdR were more similar to those of TSA than to
DNMT1,
DNMT3B, or double
DNMT somatic cell knockout. Furthermore, the effects of 5-aza-CdR were similar at one and five days exposure, suggesting active demethylation or direct influence of both drugs on the stability of methylation and/or chromatin marks. Agents that induce gene activation through hypomethylation may have unintended consequences, since nearly as many genes were downregulated as upregulated after demethylation. In addition, a 75 kb cluster of metallothionein genes was coordinately regulated.
We develop for the first time a new electrochemical biosensor for signal-on detection of T4 polynucleotide kinase (PNK) based on the enhanced quasi-reversible redox signal of prussian blue generated ...by self-sacrificial label of iron metal-organic framework (FeMOF). The DNA hairpin probe modified with FeMOF@AuNPs at the 3’-thiol end acts as the substrate of PNK. The presence of PNK enables the 5’-phosphorylation of hairpin probe, which may subsequently function as the substrate of lambda exonuclease. Lambda exonuclease removes the 5’ mononucleotides from the stem, unfolding the hairpin structure and releasing the single-stranded DNA (ssDNA). The resultant FeMOF@AuNP-modified ssDNA may specifically hybridize with the capture probe to form the double-strand DNA (dsDNA) duplex, enabling the immobilization of FeMOF on the electrode surface. The reaction of Fe3+ in the MOF with K4Fe(CN)6 leads to the formation of prussian blue on the electrode surface and consequently the generation of a high electrochemical signal. This assay is very simple without the involvement of the pre-synthesized prussian blue which is unstable in neutral buffer, and the self-sacrificial label of FeMOF can achieve great signal amplification without the involvement of any extra functional materials. Due to the introduction of self-sacrificial label of FeMOF and the formation of prussian blue nanolayers with good quasi-reversible cyclic voltammetric electrochemical activity, this biosensor exhibits high sensitivity and a large dynamic range. Moreover, this biosensor can be used to screen the PNK inhibitors, holding great potential in disease diagnosis and drug discovery.
•We develop a new electrochemical biosensor for signal-on detection of T4 polynucleotide kinase (PNK).•This electrochemical biosensor is based on the enhanced quasi-reversible redox signal of prussian blue generated by self-sacrificial label of iron metal-organic framework (FeMOF).•This assay is very simple without the involvement of the pre-synthesized prussian blue which is unstable in neutral buffer.•The self-sacrificial label of FeMOF can achieve great signal amplification without the involvement of any extra functional materials.
PDF
