Chao Lu

The identification of an ESCC susceptibility SNP rs920778 that regulates the expression of lncRNA HOTAIR via a novel intronic enhancer

Long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR), which could induce genome-wide retargeting of polycomb-repressive complex 2, trimethylates histone H3 lysine-27 (H3K27me3) and deregulation of multiple downstream genes, is involved in development and progression of esophageal squamous cell carcinoma (ESCC). We hypothesized that the functional single nucleotide polymorphisms (SNP) in HOTAIR may affect HOTAIR expression and/or its function and, thus, ESCC risk. Therefore, we examined the association between three haplotype-tagging SNPs (htSNP) across the whole HOTAIR locus and ESCC risk as well as the functional relevance of an ESCC susceptibility SNP rs920778. Genotypes were determined in three independent case-control sets consisted of 2098 ESCC patients and 2150 controls. The allele-specific regulation on HOTAIR expression by the rs920778 SNP was investigated in vitro and in vivo. We found that the HOTAIR rs920778 TT carriers had a 1.37-fold, 1.78-fold and 2.08-fold increased ESCC risk in Jinan, Shijiazhuang and Huaian populations, respectively, compared with the CC carriers (P = 0.003, 7.7 × 10(-4) and 5.9 × 10(-4)). During inspecting functional relevance of the rs920778 SNP, we identified a novel intronic HOTAIR enhancer locating between +1719bp and +2353bp from the transcriptional start site through reporter assays. Moreover, there is an allelic regulation of rs920778 on HOTAIR expression via this enhancer in both ESCC cell lines and normal esophageal tissue specimens, with higher HOTAIR expression among T allele carriers. These results demonstrate that functional genetic variants influencing lncRNA regulation may explain a fraction of ESCC genetic basis.

Synthesis and Design of Aggregation-Induced Emission Surfactants: Direct Observation of Micelle Transitions and Microemulsion Droplets

The direct visualization of micelle transitions is a long-standing challenge owing to the intractable aggregation-caused quenching of light emission in the micelle solution. Herein, we report the synthesis of a surfactant with a tetraphenylethene (TPE) core and aggregation-induced emission (AIE) characteristics. The transition processes of surfactant micelles and the microemulsion droplets (MEDs) formed by the surfactant with a TPE core were clearly visualized by a high-contrast fluorescence imaging method. The fluorescence intensity of the MEDs decreased as the size of MEDs increased as a result of weakening of the restriction of intramolecular rotation (RIR). The results of this study deepen our understanding of micelle-transition processes and provide solid evidence in favor of the hypothesis that the AIE phenomenon has its origin in the RIR of fluorophores in the aggregate state.

Association of a Genetic Variation in a miR-191 Binding Site in MDM4 with Risk of Esophageal Squamous Cell Carcinoma

As an oncoprotein, MDM4 plays a key part in P53 tumor suppressor pathway through negatively regulating P53 function. It has been reported that an rs4245739 A>C polymorphism locating in the MDM4 3′-untranslated region creates a miR-191 target site and results in decreased MDM4 expression. Therefore, we investigated the association between this polymorphism and esophageal squamous cell carcinoma (ESCC) risk as well as its biological function in vivo. Genotypes were determined in two independent case-control sets consisted of 1128 ESCC cases and 1150 controls from two regions of China. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. The impact of the polymorphism on MDM4 expression was examined with esophagus tissues. Our results demonstrated that the MDM4 rs4245739 AC and CC genotypes were significantly associated with decreased ESCC risk compared with the AA genotype in both case-control sets (Jinan set: ORu200a=u200a0.54, 95% CIu200a=u200a0.35–0.82, Pu200a=u200a0.004; Huaian set: ORu200a=u200a0.68, 95% CIu200a=u200a0.45–0.99, Pu200a=u200a0.049). Stratified analyses revealed that a multiplicative interaction between rs4245739 and smoking or drinking was evident (Gene-smoking: P interactioinu200a=u200a0.022; gene-drinking: P interactioinu200a=u200a0.032). After detecting In vivo MDM4 mRNA expression, we found that the rs4245739 AC and CC genotype carriers had significantly decreased MDM4 expression in normal esophagus tissues compared with AA genotype carriers, indicating a consistent genotype-phenotype correlation. Our results elucidate that the MDM4 rs4245739 polymorphism contributes to susceptibility of ESCC and support the hypothesis that genetic variants, interrupting miRNA-mediated gene regulation, may modify cancer risk.

Aggregation-Induced Emission: A Simple Strategy to Improve Chemiluminescence Resonance Energy Transfer

The emergence of aggregation-induced emission (AIE) has opened up a new avenue for scientists. There is a great demand for the development of a new generation chemiluminescence resonance energy transfer (CRET) acceptors with AIE characteristics due to the aggregation-caused chemiluminescence (CL) quenching effect commonly observed in the conventional fluorophore CL acceptors at high concentrations. However, the systematical studies involving in AIE-amplified CL are still scarce. Herein, it is the first report that the gold nanocluster aggregates (a type of well-defined AIE molecules) are used to study their influence on the bis(2,4,6-trichlorophenyl) oxalate (TCPO)-H2O2 CL reaction. Interestingly, the AIE molecules in the diluted solution are unable to boost the CL signal of the TCPO-H2O2 system, but their aggregates display a strongly enhanced CL emission compared to their counterparts of fluorophore molecules, thanks to the unique AIE effect of gold nanoclusters. In comparison to rhodamine B with the aid of an imidazole catalyst, the detection limit of the gold nanocluster aggregate-amplified CL probe for H2O2 (S/N = 3) is low in the absence of any catalyst. Finally, the other two typical AIE molecules, Au(I)-thiolate complexes and 9,10-bis[4-(3-sulfonatopropoxyl)-styryl]anthracene (BSPSA), are investigated to verify the generality of the AIE molecule-amplified CL emissions. These results demonstrate effective access to highly fluorescent AIE molecules with practical applications in avoiding the aggregation-induced CL quenching at high concentrations, which can be expected to provide a novel and sensitive platform for the CL amplified detection.

Acetone Cataluminescence as an Indicator for Evaluation of Heterogeneous Base Catalysts in Biodiesel Production

Rapid and effective evaluation techniques for heterogeneous base catalysts in biodiesel production are highly desirable with increased global demand for biofuels. In this work, we have discovered direct connections between the number of medium-strength basic sites of heterogeneous base catalysts in biodiesel production and cataluminescence intensity in acetone aldol condensation reactions. Accordingly, acetone cataluminescence has been employed as an indicator for rapid evaluation of heterogeneous base catalysts in biodiesel production. Its practical feasibility has been first established using commercially available heterogeneous base catalysts in biodiesel production (including MgO, Al2O3, TiO2, and ZnO), indicating a good matching between the proposed cataluminescence screening method and routine temperature-programmed desorption measurements. Subsequently, the proposed cataluminescence method can be used to effectively distinguish a set of layered double hydroxides and layered double oxide with fewer differences of basic sites, and the relative standard deviation (RSD) of the proposed method is 2.90%. The developed cataluminescence platform is able to take advantage of low cost, simple configuration, fast response, long-term stability, and easy operation. This work has a great potential in distinguishing weak/strong basic sites and even acidic sites of each catalyst system by tuning molecular probes.

Fluorescence microscopy as an alternative to electron microscopy for microscale dispersion evaluation of organic-inorganic composites.

Inorganic dispersion is of great importance for actual implementation of advanced properties of organic–inorganic composites. Currently, electron microscopy is the most conventional approach for observing dispersion of inorganic fillers from ultrathin sections of organic–inorganic composites at the nanoscale by professional technicians. However, direct visualization of macrodispersion of inorganic fillers in organic–inorganic composites using high-contrast fluorescent imaging method is hampered. Here we design and synthesize a unique fluorescent surfactant, which combines the properties of the aggregation-induced emission (AIE) and amphiphilicity, to image macrodispersion of montmorillonite and layered double hydroxide fillers in polymer matrix. The proposed fluorescence imaging provides a number of important advantages over electron microscope imaging, and opens a new avenue in the development of direct three-dimensional observation of inorganic filler macrodispersion in organic–inorganic composites.

Detection of Oxygen Vacancies in Oxides by Defect-Dependent Cataluminescence.

Oxygen vacancies can control a number of distinct properties of oxides. However, rapid and simple detection of oxygen vacancies is a great challenge owing to their elusive species and highly diluted contents. In this work, we have discovered that cataluminescence (CTL) intensity in diethyl ether oxidation reaction on the surface of TiO2 nanoparticles is proportional to the content of oxygen vacancies. The oxygen vacancy-dependent diethyl ether CTL is attributed to the fact that abundant chemisorbed O2 in oxygen vacancies could facilitate its contact reaction with chemisorbed diethyl ether molecules, resulting in an obvious improvement of CTL intensity. Therefore, diethyl ether CTL can be employed as a simple probe for oxygen vacancies in TiO2 nanoparticles. Its feasibility is validated by detecting the CTL intensity of diethyl ether on the surface of TiO2 with variable oxygen vacancies by metal ion-doped TiO2 nanoparticles (Cu, Fe, Co, and Cr) and hydrogen-treated TiO2 nanoparticles at different temperatures. The content of oxygen vacancies by the present CTL probe is in good agreement with that obtained by conventional X-ray photoelectron spectroscopy (XPS) technique. The superior properties of the developed CTL probe over already-developed methods include fast response, easy operation, low cost, long-term stability, and simple configuration. We believe that the oxygen vacancy-sensitive CTL probe has a great potential in distinguishing oxygen vacancies in oxides.

Turn-On Luminescent Probes for the Real-Time Monitoring of Endogenous Hydroxyl Radicals in Living Cells.

The utilization of semiconductor quantum dots (QDs) as optical labels for biosensing and biorecognition has made substantial progress. However, the development of a suitable QD-based luminescent probe that is capable of detecting individual reactive oxygen species (ROS) represents a great challenge, mainly because the fluorescence of QDs is quenched by a wide variety of ROS. To overcome this limitation, a novel QD-based turn-on luminescent probe for the specific detection of (.) OH has been designed, and its application in monitoring the endogenous release of (.) OH species in living cells is demonstrated. Metal citrate complexes on the surfaces of the QDs can act as electron donors, injecting electrons into the LUMO of the QDs, while (.) OH can inject holes into the HOMO of the QDs. Accordingly, electron-hole pairs are produced, which could emit strong luminescence by electron-hole recombination. Importantly, this luminescent probe does not respond to other ROS.

Pharmacogenetic role of ERCC1 genetic variants in treatment response of platinum-based chemotherapy among advanced non-small cell lung cancer patients

The excision repair cross-complementation group 1 (ERCC1) plays an essential role in DNA repair and has been linked to resistance to platinum-based anticancer drugs among advanced non-small cell lung cancer (NSCLC) patients. We systematically evaluate whether ERCC1 Asn118Asn and C8092A genetic variants are associated with treatment response of platinum chemotherapy. We preformed a meta-analysis using ten eligible cohort studies (including 11 datasets) with a total of 1,252 NSCLC patients to summarize the existing data on the association between the ERCC1 Asn118Asn and C8092A polymorphisms and response to platinum regiments. Odds ratio or hazard ratio with 95% confidence interval were calculated to estimate the correlation. We found that neither ERCC1 C8092A polymorphism nor Asn118Asn variant is associated with different response of platinum-based treatment among advanced NSCLC patients. Additionally, these two genetic variants are not related to treatment response in either Caucasian patients or Asian patients. Our meta-analysis indicates that the ERCC1 Asn118Asn and C8092A polymorphisms may not be good prognostic biomarkers for platinum-based chemotherapy in patients with stage III–IV NSCLC.

Functional MDM4 rs4245739 genetic variant, alone and in combination with P53 Arg72Pro polymorphism, contributes to breast cancer susceptibility.

The oncoprotein MDM4 plays an essential role in P53 tumor suppressor pathway through negative regulation of P53 function. It has been reported that the rs4245739 Axa0>xa0C polymorphism located in the MDM4 3′-untranslated region creates a miR-191 target site and results in decreased MDM4 expression. Therefore, we investigated the association of the MDM4 rs4245739 polymorphism as well as the P53 Arg72Pro genetic variant with the breast cancer risk. Genotypes were determined in two independent case–control sets consisting of 1100 breast cancer cases and 1400 controls from two regions of China. Odds ratios (ORs) and 95xa0% confidence intervals (CIs) were estimated by logistic regression. Our results demonstrated that the MDM4 rs4245739 AC and CC genotypes were significantly associated with decreased breast cancer risk compared to the AA genotype in both the case–control sets (Jinan set: ORxa0=xa00.55, 95xa0% CI 0.40–0.76, Pxa0=xa02.3xa0×xa010−4; Huaian set: ORxa0=xa00.41, 95xa0% CI 0.25–0.67, Pxa0=xa03.1xa0×xa010−4). The P53 Arg/Pro genotype or Pro/Pro genotype was significantly associated with an increased risk of developing breast cancer, compared to the P53 Arg/Arg genotype in both the case–control sets (all Pxa0<xa00.05). Interestingly, we observed a combinational effect between MDM4 rs4245739 and P53 Arg72Pro variants in attenuating breast cancer risk, highlighting the importance of the P53 tumor suppressor pathway genes during malignant transformation. Our results also support the hypothesis that genetic variants interrupting miRNA-mediated gene regulation might be important genetic modifiers of breast cancer risk.