Clioquinol rescues yeast cells from Aß42 toxicity via the inhibition of oxidative damage.

Alzheimer's disease (AD), the most common form of dementia, has gotten considerable attention. Previous studies have demonstrated that clioquinol (CQ) as a metal chelator is a potential drug for the treatment of AD. However, the mode of action of CQ in AD is still unclear. In our study, the antioxidant effects of CQ on yeast cells expressing Aß42 were investigated. We found that CQ could reduce Aß42 toxicity by alleviating reactive oxygen species (ROS) generation and lipid peroxidation level in yeast cells. These alterations were mainly attributable to the increased reduced glutathione (GSH) content and independent of activities of superoxide dismutase (SOD) and/or catalase (CAT). CQ could affect antioxidant enzyme activity by altering the transcription level of related genes. Interestingly, it was noted for the first time that CQ could combine with antioxidant enzymes to reduce their enzymatic activities by molecular docking and circular dichroism spectroscopy. In addition, CQ restored Aß42-mediated disruption of GSH homeostasis via regulating YAP1 expression to protect cells against oxidative stress. Our findings not only improve the current understanding of the mechanism of CQ as a potential drug for AD treatment but also provide ideas for subsequent drug research and development.

Identification of Hydroxysteroid Dehydrogenase Type 1 As a Potential Bladder Tumor Marker.

Background: The 17beta-hydroxysteroid dehydrogenase type 1 (HSD17B) family has been implicated in the prognosis and treatment prediction of various malignancies; however, its association with bladder cancer (BLCA) remains unclear. This study aimed to evaluate the potential of HSD17B1, as a prognostic biomarker, for the survival of patients with BLCA and to determine its effectiveness as a supplemental biomarker for BLCA. Methods: A series of bioinformatics techniques were applied to investigate the expression of HSD17B1 in different types of cancer and its potential association with the prognosis of BLCA patients using diverse databases. The UALCAN, Human Protein Atlas, cBioPortal, Metascape, GEPIA, MethSurv, and TIMER were employed to analyze expression differences, mutation status, enrichment analysis, overall survival, methylation, and immune-infiltrating cells. The real-time reverse transcription-PCR (qRT-PCR) was implemented to detect the messenger ribonucleic acid (mRNA) expression levels of HSD17B1 in vitro. Results: Elevated mRNA and protein levels of HSD17B1, surpassing normal levels, were observed in BLCA samples. In addition, the BLCA patients with higher mRNA expression level of HSD17B1 significantly reduced the overall survival. Also, several immune infiltrating cells, including mast cell resting CIBERSORT-ABS, have been identified as tumor-associated biomarker genes, with the potential to significantly influence the immunological environment. Finally, qRT-PCR analysis revealed a significant upregulation of HSD17B1 mRNA expression level in the cancer cells compared to the human 293T cells, which was consistent with the bioinformatics data. Conclusion: There is a strong correlation between the elevated HSD17B1 expression and positive prognosis in patients with BLCA. Therefore, HSD17B1 can be used as a prognostic biomarker in these patients.

The correlation between CpG island methylation of hTERT promoter and human age prediction.

DNA methylation is an epigenetic modification that occurs during the life cycle of individuals. Its degree is closely associated with the methylation status of CpG sites in its promoter region. Based on the previous screening that the hTERT methylation is both related to tumors and age, we suspected that the age inference based on hTERT methylation would be disturbed by the disease of the tested person. Herein, eight CpG sites in the hTERT promoter region were analyzed by real-time methylation-specific PCR, and we found that CpG2, CpG5, and CpG8 were closely related to the tumor (P < 0.05). The remaining five CpG sites had a large error in predicting age alone. Combining them to establish a model yielded better results, with an average age error of 4.35 years. This study provides a reliable and accurate detection method for the DNA methylation status of multiple CpG sites on the hTERT gene promoter, which can be used for the prediction of forensic age and assistant diagnosis of clinical diseases.

A molecularly imprinted electrochemical aptasensor based on zinc oxide and co-deposited gold nanoparticles/reduced graphene oxide composite for detection of amoxicillin.

The molecularly imprinted electrochemical aptasensor was constructed based on co-deposition of zinc oxide and gold nanoparticles/reduced graphene oxide composite. Aptamer was used as a new kind of functional monomer and the aptamer-amoxicillin complex was formed by hydrogen bond. Then, the complex was fixed on the surface of the modified electrode by Au-S bond. Three-dimensional imprinted polymeric membrane was formed by electropolymerization of dopamine, and the imprinted sites with good specificity and affinity were formed after elution. Combined with the specificity of molecularly imprinted technology and the affinity of aptamer, the selective recognition of amoxicillin can be realized. Under the optimal experimental conditions, the linear range was from 10-14 to 10-8 M, and the detection limit was 3.3 × 10-15 M. The sensor exhibited satisfactory selectivity, repeatability, and stability and was successfully used for 10-9 M amoxicillin determination in real water and food samples.

Molecularly Imprinted Electrochemical Sensor Based on Nitrogen-doped Molybdenum Carbide Nanosphere for Trace Analysis of Resveratrol.

A novel molecularly imprinted electrochemical sensor based on nitrogen-doped molybdenum carbide(N-Mo2 C) nanosphere was fabricated for trace analysis of resveratrol in this work. N-Mo2 C with large specific surface area and good electrical conductivity was introduced to construct a sensitive imprinting platform. Molecularly imprinted polymer film was prepared through a simple electropolymerization method using resveratrol as the template molecule and o-phenylenediamine as the functional monomer. The sensor shows great analytical performance in the concentration range of 10-9  mol L-1 to 10-4  mol L-1 and the detection limit is as low as 4.37×10-10  mol L-1 . The sensor also has the advantages of good selectivity, reproducibility and stability, which opens a new way for the application of molecularly imprinted electrochemical sensors in the field ofbiomedicine detection.

A FRET Fluorescent Sensor for Ratiometric and Visual Detection of Sulfide Based on Carbon Dots and Silver Nanoclusters.

In this work, the fluorescent sensor based on fluorescence resonance energy transfer (FRET) and electrostatic interaction (EI) was prepared for the ratiometric and visual detecting S2-. The FRET fluorescent sensor consists of two fluorophores, with carbon dots (CDs) as energy donors and silver nanoclusters (Ag NCs) as acceptors. At 390 nm excitation, CDs and Ag NCs showed two well-separated peaks at 445 nm and 660 nm, separately. The existence of S2- caused the red fluorescence at 660 nm to be quenched, whereas the blue fluorescence at 445 nm was restored, and the fluorescence color of the ratiometric sensor changed from pink to blue. It could be employed in ratiometric and visual detecting S2-. The linear range of quantitative detection S2- was 0.5-100 µM, and its detection limit was 0.35 µM. CDs-Ag NCs could be used for detecting S2- in mineral water and tap water. The results showed that the FRET ratiometric fluorescent sensor exhibits good anti-interference and high selectivity for detecting S2- in environmental water samples.

Near-infrared carbon dots for cell imaging and detecting ciprofloxacin by label-free fluorescence sensor based on aptamer.

A label-free fluorescence sensor based on near-infrared carbon dots (NIR-CDs) and aptamer is described for the highly sensitive and selective detection of ciprofloxacin (CIP). NIR-CDs were synthesized from polyethyleneimine and reduced glutathione by one-step hydrothermal method. The electrostatic interaction between the positively charged carbon dots and the negatively charged aptamer resulted in fluorescence quenching. After the addition of CIP, the specific binding between CIP aptamer and CIP was stronger, resulting in fluorescence recovery. Under the optimal experimental conditions, the recovered fluorescence intensity has a linear relationship with the concentration of CIP in the range 0.5-800 ng/mL, and the detection limit is 0.167 ng/mL. The prepared carbon dots have excellent optical properties and biocompatibility, and due to their emission characteristics in the near-infrared window, they can be used for biological imaging, which has also been confirmed in the experiment. The feasibility of the label-free fluorescence sensor for the detection of CIP is also proved by confocal fluorescence imaging. The detection results of CIP determination in milk by this sensor are satisfactory, indicating that the developed sensor has great application potential.

Molecularly imprinted electrochemical aptasensor based on functionalized graphene and nitrogen-doped carbon quantum dots for trace cortisol assay.

This paper proposes a novel electrochemical aptasensor that integrates molecular imprinting techniques for trace analysis of cortisol. This sensor is based on functionalized graphene and nitrogen-doped carbon quantum dots. The morphology and structure of the modified electrode were characterized by scanning electron microscopy and Raman spectroscopy. The functional monomer aptamer and the template molecule cortisol were adsorbed on the electrode by electrostatic adsorption to construct an imprinted sensing platform. Under the optimal conditions, such as the concentration of template molecule, the ratio of template to functional monomer, the elution and adsorption time, the sensor exhibits linearity and a low detection limit of 10-12-10-8 M and 3.3 × 10-13 M, which is more sensitive than other reported cortisol analysis methods. In addition, this sensor can realize the determination of cortisol in salivary samples with high recovery values, showing great development potential in the field of life sciences.

A Significant Fluorescent Aptamer Sensor Based on Carbon Dots and Graphene Oxide for Highly Selective Detection of Progesterone.

In this paper, a fluorescent aptamer sensor was constructed based on the carbon dots (CDs) and graphene oxide (GO). This sensor combines the excellent fluorescence performance of CDs with the high specificity of aptamer, which can detect progesterone (P4) with high sensitivity and selectivity. In the absence of P4, the CDs-aptamer system and GO form a fluorescence resonance energy transfer process (FRET), which quenches the fluorescence of the CDs. When P4 is added, the aptamer specifically binds to it, resulting the fluorescence of the CDs is recovered. At optimal conditions, the fluorescence intensity recovered by the CDs has a linear relationship with the concentration of P4 in the range of 0.1-120 nM and the detection limit is 3.3 × 10-11 M. Besides, the sensor has satisfactory detection results of P4 in milk, indicating that constructed method has enormous potential for application in food safety.

A novel molecularly imprinted electrochemical sensor based on a nitrogen-doped graphene oxide quantum dot and molybdenum carbide nanocomposite for indometacin determination.

In this work, nitrogen-doped graphene oxide quantum dots (N-GOQDs) were embedded into Mo2C to prepare a nanocomposite with great electrical conductivity and a large specific surface area. We manufactured an innovative electrochemical sensor based on N-GOQDs-Mo2C and a molecularly imprinted polymer (MIP) for the highly sensitive detection of indometacin (IDMC). The MIP was synthesized by electropolymerization using acrylamide as the functional monomer and IDMC as the template molecule. N-GOQDs-Mo2C was organized by an elementary hydrothermal approach and characterized by SEM, TEM, XRD and FT-IR. In the first-rank experimental conditions, the MIP electrochemical sensor shows a wide linear range from 10-15 M to 10-5 M for IDMC detection and the detection limit is as low as 9.508 × 10-16 M. Additionally, the manufactured sensor shows great selectivity for indometacin, excellent repeatability and stableness. The sensor can be applied to the detection of indometacin in tablets and water samples with fulfilling consequence.

A sensitive molecularly imprinted electrochemical aptasensor for highly specific determination of melamine.

An electrochemical aptamer sensor based on gold nanoparticles (AuNPs) was developed for highly specific sensing of melamine (MEL), which combines molecularly imprinted polymers (MIPs) and aptamers. AuNPs were synthesized by simple reduction of sodium citrate and characterized by transmission electron microscopy. The MIP membranes with particular recognition sites were formed by electropolymerization of dopamine (DA) with polythymine (poly T) aptamers as functional monomers and melamine as template molecules. Under optimal experimental conditions, this molecularly imprinted electrochemical aptamer sensor (MIEAS) exhibits a linear relationship between 10-12 M and 10-4 M for detecting MEL with the detection limit of 6.7 × 10-13 M. Moreover, this sensor displays excellent selectivity, reproducibility and stability. The milk samples analysis has confirmed the potential application of this MIEAS to quantitative detection of melamine.

A Fluorescent "Turn-off" Probe for the Determination of Curcumin Using Upconvert Luminescent Carbon Dots.

This work established a novel and simple method for quantitative determination of curcumin by developing a "turn-off" fluorescence probe based on upconvert luminescent carbon dots (p-CDs). The carbon dots were synthesized with p-aminobenzoic acid (PABA) and ethanol by solvothermal method and had specific up-conversion luminescence properties which could be applied in other sensing fields. The sensing mechanism of this fluorescent probe was based on the inter filter effect (IFE) between p-CDs and curcumin. As the concentration of curcumin increased, the fluorescence of p-CDs could be selectively quenched. Under the optimal conditions, the fluorescence quenching intensity of p-CDs had a good linear relationship with curcumin in the range of 0.4-45 µΜ and the detection limit was 0.133 µM. In addition, the fluorescent "turn-off" probe constructed with p-CDs exhibited high accuracy and recovery in the analysis of real sample curry powder, indicating that the fluorescence "turn-off" probe had potential application for the detection of curcumin in the complex matrixes.