A novel dual-mode aptasensor based colorimetry and electrochemical detection of norovirus in fecal sample.

Norovirus is a leading cause of acute gastroenteritis in humans. This paper presents the development of a novel dual-mode aptasensor for detecting norovirus using colorimetry and electrochemical methods. The initial colorimetric method utilizes gold nanoparticles (AuNPs) and sodium chloride to establish a positive correlation between the concentration of norovirus in a solution and the absorbance ratio A650/A520. The naked eye can detect concentrations as low as 0.1 µg/mL, corresponding to a Ct value of 33 (2.2 copies/µL, CT = 34.102-3.2185·lgX), allowing for qualitative and semi-quantitative analysis. For more accurate trace analysis, a gold electrode is modified with a thiol-modified aptamer and closed with 6-Mercapto-1-hexanol. After incubation with norovirus, the virus specifically binds to the aptamer, causing changes in its spatial structure and distance from the electrode surface. These changes can then be detected using electrochemical square wave voltammetry (SWV). Under optimal reaction conditions, the peak current from SWV exhibits a strong linear relationship with the logarithm of norovirus concentrations between 10-9 µg/mL and 10-2 µg/mL. The regression equation Y = 14.76789 + 1.03983·lgX, with an R2 value of 0.987, accurately represents this relationship. The limit of detection was determined to be 1.365 × 10-10 µg/mL. Furthermore, the aptasensor demonstrated high specificity for norovirus in fecal samples, making it a promising tool for detecting norovirus in various sample types.

Comparison of UV-induced AOPs (UV/Cl2, UV/NH2Cl, UV/ClO2 and UV/H2O2 ) in the degradation of iopamidol: Kinetics, energy requirements and DBPs-related toxicity in sequential disinfection processes.

The UV-induced advanced oxidation processes (AOPs, including UV/Cl2, UV/NH2Cl, UV/ClO2 and UV/H2O2 ) degradation kinetics and energy requirements of iopamidol as well as DBPs-related toxicity in sequential disinfection were compared in this study. The photodegradation of iopamidol in these processes can be well described by pseudo-first-order model and the removal efficiency ranked in descending order of UV/Cl2  > UV/H2O2  > UV/NH2Cl > UV/ClO2  > UV. The synergistic effects could be attributed to diverse radical species generated in each system. Influencing factors of oxidant dosage, UV intensity, solution pH and water matrixes (Cl- , NH4 + and nature organic matter) were evaluated in detail. Higher oxidant dosages and greater UV intensities led to bigger pseudo-first-order rate constants (Kobs) in these processes, but the pH behaviors exhibited quite differently. The presence of Cl- , NH4 + and nature organic matter posed different effects on the degradation rate. The parameter of electrical energy per order (EE/O) was adopted to evaluate the energy requirements of the tested systems and it followed the trend of UV/ClO2  > UV > UV/NH2Cl > UV/H2O2  > UV/Cl2 . Pretreatment of iopamidol by UV/Cl2 and UV/NH2Cl clearly enhanced the production of classical disinfection by-products (DBPs) and iodo-trihalomethanes (I-THMs) during subsequent oxidation while UV/ClO2 and UV/H2O2 exhibited almost elimination effect. From the perspective of weighted water toxicity, the risk ranking was UV/NH2Cl > UV/Cl2 > UV > UV/H2O2 > UV/ClO2 . Among the discussed UV-driven AOPs, UV/Cl2 was proved to be the most cost-effective one for iopamidol removal while UV/ClO2 displayed overwhelming advantages in regulating the water toxicity associated with DBPs, especially I-THMs. The present results could provide some insights into the application of UV-activated AOPs technologies in tradeoffs between cost-effectiveness assessment and DBPs-related toxicity control of the disinfected waters containing iopamidol.

Antitumour bioactive peptides isolated from marine organisms.

Marine organisms are an important source of antitumour active substances. Thus, pharmaceutical research in recent years has focused on exploring new antitumour drugs derived from marine organisms, and, many peptide drugs with strong antitumour activities have been successfully extracted. Based on different mechanisms, this paper reviews the research on several typical antitumour bioactive peptides in marine drugs and the latest progress therein. Additionally, the development prospects for these antitumour bioactive peptide-based drugs are discussed so as to provide a reference for future research in this field.

Label-free fluorescent sensor for lead ion detection based on lead(II)-stabilized G-quadruplex formation.

A label-free fluorescent DNA sensor for the detection of lead ions (Pb(2+)) based on lead(II)-stabilized G-quadruplex formation is proposed in this article. A guanine (G)-rich oligonucleotide, T30695, was used as a recognition probe, and a DNA intercalator, SYBR Green I (SG), was used as a signal reporter. In the absence of Pb(2+), the SG intercalated with the single-stranded random-coil T30695 and emitted strong fluorescence. While in the presence of Pb(2+), the random-coil T30695 would fold into a G-quadruplex structure and the SG could barely show weak fluorescence, and the fluorescence intensity was inversely proportional to the involving amount of Pb(2+). Based on this, a selective lead ion sensor with a limit of detection of 3.79 ppb (parts per billion) and a detection range from 0 to 600 ppb was constructed. Because detection for real samples was also demonstrated to be reliable, this simple, low-cost, sensitive, and selective sensor holds good potential for Pb(2+) detection in real environmental samples.

Colourimetric and SERS dual-mode aptasensor using Au@Ag and magnetic nanoparticles for the detection of Campylobacter jejuni.

A dual-mode aptasensor has been developed for the effective detection of Campylobacter jejuni (C. jejuni), a major cause of gastrointestinal disease worldwide. The aptasensor utilizes nanoparticles, specifically a core-shell structure consisting of gold and silver (Au@Ag NPs), along with magnetic nanoparticles (MNPs). When Campylobacter jejuni is introduced, "Au@Ag NPs-Aptamer-Campylobacter jejuni-Aptamer-MNPs" sandwich complexes are formed due to the high affinity of the aptamer for the bacterial surface membrane proteins. The dual-mode aptasensor can magnetically enrich the sample in just 15 min, and the presence of Campylobacter jejuni is determined by observing a color change. Additionally, the concentration of Campylobacter jejuni can be quantified using surface-enhanced Raman spectroscopy (SERS) and standard curves. This results in a wider linear range (1.8 × 101-108 CFU/mL) under optimal conditions, a lower limit of detection (6 CFU/mL), and a higher selectivity for the detection of bacteria compared to previously reported sensors. Compared with traditional microbial culture counting methods, the dual-mode aptasensor does not require Raman reporters. The physical action of magnetic enrichment, along with the application of Au@Ag NPs, improves the accuracy of the dual-mode aptasensor, offering the advantages of convenience and high sensitivity. Moreover, by utilizing different types of aptamers, this aptasensor can be modified to detect a wider range of harmful pathogens in various environments.

Corrigendum to "Suppression of IL-6 Gene by shRNA Augments Gemcitabine Chemosensitization in Pancreatic Adenocarcinoma Cells".

[This corrects the article DOI: 10.1155/2018/3195025.].

Plasmonic tunable Ag-coated gold nanorod arrays as reusable SERS substrates for multiplexed antibiotics detection.

Antibiotic contaminants in aqueous media pose a serious threat to human and ecological environments. Therefore, it is necessary to develop robust strategies to detect antibiotic residues. For this purpose, a self-assembly and in situ electrochemical reduction method is utilized to tailor silver nanoparticles (AgNPs)-coated GNRs (AgNPs/GNRs) large-scale vertical arrays. These AgNPs/GNRs arrays exhibit outstanding surface-enhanced Raman scattering (SERS) activities because of abundant Raman hot-spots among the adjacent AgNPs and GNRs, but also excellent stability and reproducibility due to the close-packed arrayed nanostructure. These remarkable features validate this arrayed substrate for high-sensitivity 4-aminothiophenol analysis with a detection limit of 0.35 pM and self-cleaning via electrochemical stripping of the adsorbed analytes and AgNPs from the GNRs arrays, therefore realizing renewable SERS applications. Moreover, the distinct SERS performance of AgNPs/GNRs arrays is verified via the analysis of multiplexed antibiotics at tens of picomolar level and no apparent changes of SERS activities are observed when recyclability is explored. The result demonstrates that the proposed AgNPs/GNRs arrays provide a novel strategy for avoiding conventional, disposable SERS substrates, as well as expanding SERS applications for simultaneous sensing and stripping of environmental contaminants.

Identification of pancreatic cancer type related factors by Weighted Gene Co-Expression Network Analysis.

This study aims to identify the core modules associated with pancreatic cancer (PC) types and the ncRNAs and transcription factors (TFs) that regulate core module genes by weighted gene co-expression network analysis (WGCNA). WGCNA was used to analyze the union of genes related to PC in NCBI and OMIM databases and the differentially expressed genes screened by TCGA-PAAD database. Samples were clustered according to gene expression in gene modules and Fisher exact method was performed. GO and KEGG were used for enrichment analysis to visually display module genes and screen driver genes. Hypergeometric test method was used to calculate pivot nodes among ncRNAs, TFs and mRNA based on RAID 2.0 and TRRUST v2 databases. The blue and yellow modules were identified as the core modules associated with PC types. MST1R, TMPRSS, MIR198, SULF1, COL1A1 and FAP were the core genes in the modules. Hypergeometric test results showed that ANCR, miR-3134, MT1DP, LOC154449, LOC28329 and other ncRNAs were key factors driving blue module genes, while LINC-ROR, UCA1, SNORD114-4, HEIH, SNORD114-6 and other ncRNAs were key factors driving yellow module genes. TFs with significant regulatory effect on blue module included LCOR, PIAS4, ZEB1, SNAI2, SMARCA4, etc. and on yellow module included HOXC6, PER2, HOXD3, TWIST2, VHL, etc. The core modules associated with PC types were proved as yellow and blue modules, and important ncRNAs and TFs regulating yellow and blue modules were found. This study provides relevant evidence for further identification of PC types.

Small cell carcinoma of the bladder: the characteristics of molecular alterations, treatment, and follow-up.

Small cell carcinoma of the bladder (SCCB) is a rare disease associated with high invasiveness and mortality. Histologically, SCCB is difficult to distinguish from small cell lung cancer (SCLC); however, it shares more similar molecular alterations with urothelial carcinoma (UC). As a result, now, the widely accepted theory about the cells of origin is that SCCB and UC probably have a common clone origin. Even the former probably comes from a preexisting UC. At present, given its rarity, early diagnoses, treatments, and follow-ups are not well established, which are vital to patients with SCCB. Inspirationally, in recent years, with the development of molecular diagnostic methods, molecular alterations of SCCB have been understood partially, which are propitious to excavate new potential therapeutic strategies and establish sound follow-ups. Therefore, the future will be light for patients with SCCB.

Efficacy and safety of gemcitabine plus anti-angiogenesis therapy for advanced pancreatic cancer: a systematic review and meta-analysis of clinical randomized phase III trials.

Purpose: Pancreatic cancer is a common digestive neoplasm with a high fatality rate. We performed this systematic review and meta-analysis of clinical randomized phase III trials to explore the efficacy and safety of gemcitabine plus anti-angiogenesis therapy versus gemcitabine monotherapy for locally advanced or metastatic pancreatic cancer. Methods: We searched PubMed, Embase and the Cochrane Library to identify eligible studies. Data were collected for the period from January 1, 2000 to August 20, 2018. Hazard ratios (HRs) and odds ratios (ORs) were used as main evaluation parameters. Results: A total of eight eligible studies with 3,586 individuals were included in the present meta-analysis. The results showed that the combination of gemcitabine plus anti-angiogenesis therapy had a significant effect on progression-free survival (HR = 0.92, 95% CI: 0.86 - 1.00, P = 0.04), but led to no significant difference in the overall survival (HR = 0.96, 95% CI: 0.88 - 1.05, P = 0.38). In terms of safety, gemcitabine plus anti-angiogenesis therapy did not increase the rate of grade 3-4 common adverse effects except for hypertension. Conclusions: Although gemcitabine plus anti-angiogenesis therapy might prolong the progression-free survival in locally advanced or metastatic pancreatic cancer, these successful results did not translate into a significant improvement in the overall survival or change in the clinical guidelines.

Photochemical degradation of iodate by UV/H2O2 process: Kinetics, parameters and enhanced formation of iodo-trihalomethanes during chloramination.

In this paper, it was demonstrated that UV/H2O2 process can not only obviously promote the degradation rate of IO3-, but also greatly enhance iodo-trihalomethanes (I-THMs) formation in sequential chloramination. UV/H2O2 exhibited much faster IO3- decomposition than either UV or H2O2 treatment alone due to the contribution of highly reactive species including O-, OH and eaq-. The degradation rate of IO3- was affected by H2O2 dosages, pH, UV intensity as well as the presence of natural organic matter (NOM). The calculated pseudo-first order rate constant gradually increased with H2O2 dosages and solution pH, but behaved directly proportional to the UV intensity. Although NOM remarkably reduced the degradation rate of IO3- in UV/H2O2 process, their presence greatly enhanced the formation of I-THMs during subsequent chloramination. The overwhelming majority of iodoform at high UV fluences was also observed, which indicated improved iodination degrees of the detected I-THMs. UV/H2O2 was proved to be more capable on the evolution of IO3- to I- as well as I-THMs than UV and thereby enhanced the toxicity of disinfected waters in the following chloramination process. This study was among the first to provide a comprehensive understanding on the transformation of IO3- as the emerging iodine precursor to form I-THMs via diverse advanced oxidation process technologies like UV/H2O2.

Diagnostic Value of CA 19-9 and Carcinoembryonic Antigen for Pancreatic Cancer: A Meta-Analysis.

BACKGROUND: CA 19-9 and carcinoembryonic antigen (CEA) are widely used for the diagnosis of pancreatic cancer. The purpose of the present study was to compare the diagnostic value of CA 19-9 with CEA for pancreatic cancer. METHODS: The studies were obtained from electronic searches conducted in PubMed, Embase, and Cochrane Library databases until December 2017. The keywords included diagnosis of pancreatic cancer, CA 19-9, and CEA. The ratio of sensitivity, the specificity, the diagnostic odds ratio (DOR), and the summary of the receiver operating characteristic (SROC) with regard to CA 19-9 and CEA were measured using the random effects model. The current study included 13 studies that comprised 4,537 participants and 1,277 patients with pancreatic cancer. RESULTS: The levels of CA 19-9 for use for the detection of pancreatic cancer were associated with higher sensitivity (ratio of sensitivity: 1.54; 1.31-1.81; P < 0.001), DOR (DOR: 3.50; 95% CI: 2.24-5.45; P < 0.001), and AUC (ratio of AUC: 1.24; 95% CI: 1.15-1.33; P < 0.001) compared with the variable CEA, while no significant difference between CA 19-9 and CEA was noted with regard to specificity (ratio of specificity: 0.97; 95% CI: 0.89-1.06; P = 0.517). The findings of the subgroup analyses suggested that different cutoff values of CA 19-9 and CEA might affect the diagnostic value. CONCLUSIONS: The findings of the present study indicated that CA 19-9 levels were associated with higher sensitivity, DOR, and AUC compared with the corresponding levels of CEA with regard to the diagnosis of pancreatic cancer.

Suppression of IL-6 Gene by shRNA Augments Gemcitabine Chemosensitization in Pancreatic Adenocarcinoma Cells.

Pancreatic adenocarcinoma has an exceedingly poor prognosis, accounting for five-year survival of less than 5%. Presently, improving the efficacy of pancreatic adenocarcinoma treatment has been the focus of medical researchers worldwide. Recently, it has been suggested that deregulation of interleukin- (IL-) 6 is caused by a key gene involved in the beginning and development of pancreatic adenocarcinoma. Herein, we investigated whether suppression of IL-6 could augment gemcitabine sensitivity in the PANC-1 cells. We found considerably higher expression of IL-6 in pancreatic adenocarcinoma tissues than that in the adjacent nontumorous tissues. Suppression of IL-6 by shRNA resulted in apoptosis as well as inhibition of cell proliferation and tumorigenicity. In addition, suppression of IL-6 remarkably promoted antitumor effect of gemcitabine, indicating that the combination of shRNA targeting IL-6 with gemcitabine may provide a potential clinical approach for pancreatic cancer therapy.

A simple fluorescent assay for cyromazine detection in raw milk by using CYR-stabilized G-quadruplex formation.

A rapid biosensor for the detection of cyromazine in milk is reported based on a fluorescence quenching result. When an FAM labelled G-rich ssDNA Tcy2 is treated with cyromazine, it can form a G-quadruplex-CYR complex and cause a change in fluorescence. As a result, the presence of cyromazine can be determined by fluorescence quenching. This sensor is selective for the detection of cyromazine in raw milk and has a limit of detection of 0.68 ppb and a detection range from 0 to 200 ppb.

Histone deacetylase 2 regulates doxorubicin (Dox) sensitivity of colorectal cancer cells by targeting ABCB1 transcription.

PURPOSE: Histone deacetylases (HDACs) have been shown to regulate cell cycle, differentiation, and apoptosis of colorectal cancer (CRC) cells, while their roles in drug sensitivity remain unclear. The objectives of the present study were to investigate the effects of HDAC2 on drug resistance of CRC cells. METHODS: We measured the expression of class I HDACs (HDAC1, 2, 3, 8) in CRC and human normal colonic epithelial cells. Additionally, we inhibited HDAC2 via siRNA or overexpressed it via pcDNA/HDAC2 transfection to evaluate its roles in doxorubicin (Dox) sensitivity. RESULTS: Our present study showed HDAC2 was significantly increased in CRC cell lines as compared to human normal colonic epithelial cells. Silencing of HDAC2 can obviously enhance the sensitivity of HCT-116 and SW480 cells to dDox. Further, knockdown of HDAC2 can significantly (p < 0.05) downregulate the expression of ABCB1, while not ABCG2, ABCC1, ABCA1, or ABCC2. Inhibition of HDAC2 decreased ABCB1 promoter activities and the phosphorylation of c-fos and c-Jun, which can directly interact with the ABCB1 promoter and then promote its transcription. Overexpression of HDAC2 by pcDNA/HDAC2 transfection significantly increased the sensitivity of CRC cells to Dox and upregulated the levels of P-gp, p-c-fos, and p-c-Jun. CONCLUSIONS: Our data revealed that HDAC2 can regulate Dox sensitivity of CRC cells by targeting ABCB1 transcription. It suggested that HDAC2 might be an important target for CRC therapy. Further, the combination of HDAC2-specific inhibitor and anticancer drugs including Dox might be an efficiency approach to elevate the treatment outcome of CRC.

Alcohol consumption and the neoplastic progression in Barrett's esophagus: a systematic review and meta-analysis.

PURPOSE: In the developed countries, the incidence of esophageal adenocarcinoma (EAC) is increasing over recent decades. The purpose of this meta-analysis was to arrive at quantitative conclusions about the contribution of alcohol intakes and the progression of Barrett's esophagus. METHODS: A comprehensive, systematic bibliographic search of medical literature published up to Oct 2013 was conducted to identify relevant studies. A meta-analysis was conducted for alcohol consumption on the Barrett's esophagus progression. RESULTS: A total of 882 cases in 6,867 individuals from 14 observational studies were indemnified in this meta-analysis. The result of this current meta-analysis, including 10 case-control and 4 cohort studies, indicated that alcohol consumption was not associated with the neoplastic progression in Barrett's esophagus (RR, 1.17; 95% CI, 0.93-1.48). When stratified by the study designs, no significant association was detected in either high vs low group or ever vs never group. CONCLUSIONS: Alcohol drinking is not associated with risk of neoplastic progression in Barrett's esophagus. Further well designed studies are needed in this area.

Construction of a tumor cell-targeting non-viral gene delivery vector with polyethylenimine modified with RGD sequence-containing peptide.

The objective of the present study was to construct a novel type of non-viral gene delivery vector with high delivery efficiency and specific tumor cell-targeting ability. The CP9 peptide (CYGGRGDTP) containing Arg-Gly-Asp sequence was employed to be conjugated onto polyethylenimine (PEI) to act as the role of the targeting moiety. The chemical linker, N-succinimidyl-3-(2-pyridyldithio) propionate, was applied during the synthesis of the vector (CP9-PEI). The physicochemical characteristics of the vector were evaluated by the methods of 1H-nuclear magnetic resonance, Fourier transform infrared spectroscopy, gel retardation assay, electron microscope observation and particle size detection. HepG2 cells were used to verify the gene delivery efficiency and targeting ability by gene delivery procedure and free CP9 peptide inhibition tests. The results showed that the successful synthesis of CP9-PEI and the synthesized vector may efficiently condense plasmid DNA into round particles with diameters of ~200 nm at a polymer/pDNA ratio of 10. CP9-PEI may deliver the reporter gene into HepG2 cells with higher efficiency and the efficiency may be inhibited by the free CP9 peptide. The present study suggested that the modification of PEI with the CP9 peptide is an effective method to construct a novel tumor cell-targeting non-viral vector, and that the novel vector exhibits great prospect in the field of cancer gene therapy.

Preparation and characterization of artificial antigens for cadmium and lead.

Cadmium and lead were conjugated to two carrier proteins using a bifunctional chelator [2-(4-aminobenzyl)-diethylenetriaminepentaacetic acid] to synthesize artificial antigens for cadmium and lead. The techniques, including ultraviolet spectrometry, circular dichroism, sodium dodecyl sulfate polyacrylamide gel electrophoresis, and inductively coupled plasma optical emission spectroscopy, were utilized for characterizing the artificial antigens. The results of ultraviolet spectrometry showed characteristic absorption peak shifts between conjugates and carrier proteins. Circular dichroism resulted that the second structure of the conjugates was α-helix. The sodium dodecyl sulfate polyacrylamide gel electrophoresis results revealed the differences of band migration and molecular weight among antigens, chelator protein conjugate, and carrier proteins. The result of coupling ratios revealed that the metal content of the antigens was much higher than that of carrier proteins. These results indicated that the artificial antigens of cadmium and lead were synthesized successfully and had potential application in immunoassays of cadmium and lead ions.

Nanoparticles assembled by aptamers and crystal violet for arsenic(III) detection in aqueous solution based on a resonance Rayleigh scattering spectral assay.

Aptamer-assembled nanomaterials have captured much attention from the field of analytical chemistry in recent years. Although they have been regarded as a promising tool for heavy metal monitoring, report involving aptamer-based biosensors for arsenic detection are rare. Herein we developed a highly sensitive and selective aptamer biosensor for As(iii) detection based on a Resonance Rayleigh Scattering (RRS) spectral assay. Prior to As(iii) detection, we firstly assembled a variety of nanoparticles with different sizes via controlling the concentration of arsenic-binding aptamers in crystal violet (CV) solutions. The results of photon correlation spectroscopy (PCS) and scanning probe microscope (SPM) testified that the introduction of As(iii) had indeed changed the size of nanoparticles, which caused a great variation in the RRS intensity at 310 nm. In the presence of 100 ppb As(iii), a maximum decline in the ratio of RRS intensity was achieved for large nanoparticles assembled from 200 nM of aptamers and CV molecules, where the average size of nanoparticles had decreased from 273 nm to 168 nm. In the case of small nanoparticles, the maximum increase ratio of the RRS intensity was obtained when the concentration of aptamer was over 600 nM. Combined with an RRS spectral assay, an effective biosensor has been developed for As(iii) detection, using the above large and small nanoparticles as the target recognition element. The present biosensor has a detection limit as low as 0.2 ppb, a dynamic range from 0.1 ppb to 200 ppb, and high selectivity over other metal ions. Such an efficient biosensor will play an important role in environmental detection.