Azo Reductase Activated Magnetic Resonance Tuning Probe with "Switch-On" Property for Specific and Sensitive Tumor Imaging in Vivo.

Cancer remains a threat to human health. However, if tumors can be detected in the early stage, then the effectiveness of cancer treatment could be significantly improved. Therefore, it is worthwhile to develop more sensitive and accurate cancer diagnostic methods. Herein, we demonstrated an azo reductase (AzoR)-activated magnetic resonance tuning (MRET) probe with a "switch-on" property for specific and sensitive tumor imaging in vivo. Specifically, Gd-labeled DNA1 (DNA1-Gd) and cyclodextrin-coated magnetic nanoparticles (MNP-CD) were employed as enhancer and quencher of MRET, respectively, while DNA2, an azobenzene (Azo) group-modified aptamer (AS1411), served as a linker between enhancer and quencher to construct the MRET probe of MNP@DNA(1-2)-Gd. In tumor tissues with high-level AzoR, the T1-weighted magnetic resonance signal of the MRET probe could be restored by intelligently regulating the switch from "OFF" to "ON" after activation with AzoR, thus accurately indicating the location of the tumor accurately. Moreover, the tumor with a 4 times smaller size than that of the normal tumor model could be imaged based on the proposed MRET probe. The as-proposed MRET-based magnetic resonance imaging strategy not only achieves tumor imaging accurately but also shows promise for early diagnosis of tumors, which might improve patients' survival rates and provide an opportunity for image-guided biomedical applications in the future.

A pH-responsive magnetic resonance tuning probe for precise imaging of bacterial infection in vivo.

Accurate and sensitive detection of bacteria is essential for treating bacterial infections. Herein, a pH-responsive magnetic resonance tuning (MRET) probe, whose T1-weighted signal is activated in the bacteria-infected acid microenvironment, is developed for in situ accurately magnetic resonance imaging (MRI) of bacterial infection in vivo. The MRET probe (MDVG-1) is an assembly of paramagnetic enhancer (gadolinium-modified i-motif DNA3, abbreviated as Gd-DNA3-Gd) and the precursor of superparamagnetic quencher (DNA and vancomycin-modified magnetic nanoparticle, abbreviated as MDV). The T1-weighted signal of Gd-DNA3-Gd is quenched once the formation of MDVG-1 (MRET ON). Interestingly, the MDVG-1 probe was disassembled into the monomers of Gd-DNA3-Gd and MDV under the bacteria-infected acid microenvironment, resulting significantly enhanced T1-weighted signal at the infected site (MRET OFF). The pH-responsive MRET probe-based enhanced MRI signal and bacteria targeting significantly improve the distinction between bacterial infectious tissues and sterile inflamed tissues, which provides a promising approach for accurately detecting bacterial infection in vivo. STATEMENT OF SIGNIFICANCE: Detecting pathogenic bacteria in vivo based on magnetic resonance imaging (MRI) strategy has been exploring recently. Although various bacterial-targeted MRI probes have been developed to image bacteria in vivo, the MRI signal of these MRI probes is always "on", which inevitably generates nonspecific background MRI signals, affecting the accuracy of MRI to a certain extent. In the current study, based on the magnetic resonance tuning (MRET) phenomenon, we present a pH-responsive MRET probe (MDVG-1) with T2-weighted imaging to T1-weighted imaging switchable properties to achieve in situ precise imaging of bacterial infection in vivo.

Enzyme-Triggered Transforming of Assembly Peptide-Modified Magnetic Resonance-Tuned Probe for Highly Sensitive Imaging of Bacterial Infection In Vivo.

Confirming bacterial infection at an early stage and distinguishing between sterile inflammation and bacterial infection is still highly needed for efficient treatment. Here, in situ highly sensitive magnetic resonance imaging (MRI) bacterial infection in vivo based on a peptide-modified magnetic resonance tuning (MRET) probe (MPD-1) that responds to matrix metallopeptidase 2 (MMP-2) highly expressed in bacteria-infected microenvironments is achieved. MPD-1 is an assembly of magnetic nanoparticle (MNP) bearing with gadolinium ion (Gd3+ ) modified MMP-2-cleavable self-assembled peptide (P1 ) and bacteria-targeting peptide (P), and it shows T2 -weighted signal due to the assemble of MNP and MRET ON phenomenon between MNP assembly and Gd3+ . Once MPD-1 accumulates at the bacterially infected site, P1 included in MPD-1 is cleaved explicitly by MMP-2, which triggers the T2 contrast agent of MPD-1 to disassemble into the monomer of MNP, leading the recovery of T1 -weighted signal. Simultaneously, Gd3+ detaches from MNP, further enhancing the T1 -weighted signal due to MRET OFF. The sensitive MRI of Staphylococcus aureus (low to 104 CFU) at the myositis site and accurate differentiation between sterile inflammation and bacterial infection based on the proposed MPD-1 probe suggests that this novel probe would be a promising candidate for efficiently detecting bacterial infection in vivo.

How Human-like Behavior of Service Robot Affects Social Distance: A Mediation Model and Cross-Cultural Comparison.

Previous studies on the human likeness of service robots have focused mainly on their human-like appearance and used psychological constructs to measure the outcomes of human likeness. Unlike previous studies, this study focused on the human-like behavior of the service robot and used a sociological construct, social distance, to measure the outcome of human likeness. We constructed a conceptual model, with perceived competence and warmth as mediators, based on social-identity theory. The hypotheses were tested through online experiments with 219 participants from China and 180 participants from the US. Similar results emerged for Chinese and American participants in that the high (vs. low) human-like behavior of the service robot caused the participants to have stronger perceptions of competence and warmth, both of which contributed to a smaller social distance between humans and service robots. Perceptions of competence and warmth completely mediated the positive effect of the human-like behavior of the service robot on social distance. Furthermore, Chinese participants showed higher anthropomorphism (perceived human-like behavior) and a stronger perception of warmth and smaller social distance. The perception of competence did not differ across cultures. This study provides suggestions for the human-likeness design of service robots to promote natural interaction between humans and service robots and increase human acceptance of service robots.

Visit-to-visit variability in triglyceride-glucose index and diabetes: A 9-year prospective study in the Kailuan Study.

Instruction/Aims: It is unknown whether variability in the triglyceride-glucose index (TyG-index) is associated with the risk of diabetes. Here, we sought to characterize the relationship between TyG-index variability and incident diabetes. Methods: We performed a prospective study of 48,013 participants in the Kailuan Study who did not have diabetes. The TyG-index was calculated as ln [triglyceride (TG, mg/dL) concentration × fasting blood glucose concentration (FBG, mg/dL)/2]. The TyG-index variability was assessed using the standard deviation (SD) of three TyG-index values that were calculated during 2006/07, 2008/09, and 2010/11. We used the Cox proportional hazard models to analyze the effect of TyG-index variability on incident diabetes. Results: A total of 4,055 participants were newly diagnosed with diabetes during the study period of 8.95 years (95% confidence interval (CI) 8.48-9.29 years). After adjustment for confounding factors, participants in the highest and second-highest quartiles had significantly higher risks of new-onset diabetes versus the lowest quartile, with hazard ratios (95% CIs) of 1.18 (1.08-1.29) and 1.13 (1.03-1.24), respectively (P trend< 0.05). These higher risks remained after further adjustment for the baseline TyG-index. Conclusions: A substantial fluctuation in TyG-index is associated with a higher risk of diabetes in the Chinese population, implying that it is important to maintain a normal and consistent TyG-index.

Bacteria-Targeted MRI Probe-Based Imaging Bacterial Infection and Monitoring Antimicrobial Therapy In Vivo.

Despite the significant advances of imaging techniques nowadays, accurate diagnosis of bacterial infections and real-time monitoring the efficacy of antibiotic therapy in vivo still remain huge challenges. Herein, a self-assembling peptide (FFYEGK) and vancomycin (Van) antibiotic molecule co-modified gadolinium (Gd) MRI nanoaggregate probe (GFV) for detecting Staphylococcus aureus (S. aureus) infection in vivo and monitoring the treatment of S. aureus-infected myositis by using daptomycin (Dap) antibiotic as model are designed and fabricated. The as-prepared GFV probe bears Van molecules, making itself good bacteria-specific targeting, and the peptide in the probe can enhance the longitudinal relaxivity rate (r1 ) after self-assembly due to the π-π stacking. The study showed that, based on the GFV probe, bacterial infections and sterile inflammation can be discriminated, and as few as 105 cfu S. aureus can be detected in vivo with high specificity and accurately. Moreover, the T1 signal of GFV probe at the S. aureus-infected site in mice correlates with the increasing time of Dap treating, indicating the possibility of monitoring the efficacy of antibacterial agents for infected mice based on the as proposed GFV probe. This study shows the potential of GFV probe for diagnosis, evaluation, and prognosis of infectious diseases in clinics.

Intracellular Pathogen Detection Based on Dual-Recognition Units Constructed Fluorescence Resonance Energy Transfer Nanoprobe.

The intracellular invasion and survival of a pathogen like Staphylococcus aureus (S. aureus) within host cells enable them to resist antibiotic treatment and colonize long-term in the host, which leads to a series of clinical issues. Rapid and specific detection of intracellular bacteria is important in diagnosis of infection and guiding antibiotic administration. Herein, this work reports a simple one-step fluorescence resonance energy transfer (FRET) platform-based strategy to achieve specific and rapid detection of S. aureus in specimens of phagocytic cells. The aptamer modified quantum dots (Aptamer-QDs) and antibiotic molecule of Teicoplanin functionalized-gold nanoparticles (Teico-AuNPs) dual-recognition units to S. aureus are employed as energy donor and acceptor, respectively. Based on the "off" to "on" signal readout mode, when in the presence of target S. aureus, the donor and acceptor are close to each other and bring high FRET efficiency, which is suitable for analysis of intracellular S. aureus. After it was incubated with the sample for 2 h, the as-prepared FRET sensor showed selectivity to the target S. aureus, and the changed fluorescence signal shows an obvious variation with increasing concentration of S. aureus in pure buffer. When the FRET strategy was further applied to assay intracellular S. aureus, there was an obvious fluorescence signal change obtained both by spectrum analysis and visual fluorescence microscope observation when the average number of S. aureus in one host cell (NS. aureus/cell) was as low as 1, which can be attributed to the high fluorescence quenching efficiency of about 41.3%. It could be envisioned that this FRET nanoprobe with high fluorescence quenching efficiency may provide a simple approach for the facile, selective, and rapid diagnosis of an intracellular bacterial infection.

The migration of acetochlor from feed to milk.

Acetochlor has been widely used globally for its effective weed control, but the dietary intake of associated residues by people has become a major concern nowadays. Milk is regarded as the best solvent to dissolve pesticides due to its fat-rich characteristic. In this study, we aimed to evaluate the transfer of acetochlor from feed to raw milk. Twenty lactating Australian Holstein cows were randomly chosen and divided into 1 control group and 3 treatment groups, feeding acetochlor at the dosages of 0, 0.45, 1.35 and 4.05 g per day during the treatment period. The concentration of acetochlor residues in raw milk was detected by QuEChERS together with a gas chromatography-mass spectrometry (GC-MS) method. The results showed that the highest concentrations of acetochlor residues in raw milk for the three treatment groups had a positive correlation with the dosage levels and the transfer efficiency of the low dose group was only 0.080%, higher than those of the other two groups. Besides, the national estimated daily intake (NEDI) of acetochlor from milk is 1.67 × 10-5 mg kg-1, which is 0.08% of the ADI. Overall, we concluded that the risk of acetochlor residues in milk was low, but high-dose acetochlor had a larger impact on milk quality and low-dose acetochlor had potential risks.

Magnetism-Resolved Separation and Fluorescence Quantification for Near-Simultaneous Detection of Multiple Pathogens.

In the modern era of molecular evidence-based medicine and advanced biomedical technologies, the rapid, sensitive and specific assay of multiple pathogens is critical to, but largely absent from, clinical practice. Therefore, to improve the current ordinary separation and collection method, we report herein a strategy of magnetism-resolved separation and fluorescence quantification for near-simultaneous detection of multiple pathogens, followed by the direct antimicrobial susceptibility testing (AST). To accomplish this strategy, we utilized aptamer-modified fluorescent-magnetic multifunctional nanoprobes (apt-FMNPs). FMNPs with intriguing different magnetic responses and excellent fluorescence quality were first self-assembled based on metal coordination interaction using (3-mercaptopropyl) trimethoxysilane, magnetic γ-Fe2O3, and fluorescent quantum dots as matrix components. Then, aptamers, which specific to target pathogens of Escherichia coli O157:H7 ( E. coli) and Salmonella typhimurium ( S. typ), were conjugated with FMNPs to yield apt-FMNPs nanoprobes for multiple pathogens assay. Based on the discrepant magnetic response of pathogen@nanoprobes complex under the identical external magnetic field, the model bacteria were fished out by magnetic adsorption at different time points and subjected to fluorescence quantification with good linear ranges and detection limits within 1h. Multiple pathogens spiked in real samples were also effectively detected by the apt-FMNPs and sequentially fished out for AST assay, which showed similar results to that for pure pathogens. The apt-FMNPs-based strategy of near-simultaneous detection of multiple pathogens shows promise for the potential application in the diagnosis and treatment of pathogen-related infectious diseases.

Selective and sensitive detection of lysozyme based on plasmon resonance light-scattering of hydrolyzed peptidoglycan stabilized-gold nanoparticles.

The simple, economic, rapid, and sensitive detection of lysozyme has an important significance for disease diagnosis since it is a potential biomarker. In this work, a new detection strategy for lysozyme was developed based on the change of the plasmon resonance light scattering (PRLS) signal of peptidoglycan stabilized gold nanoparticles (PGN-AuNPs). Peptidoglycan (PGN) was employed as a stabilizer to prepare PGN-AuNPs which have the properties of a uniform particle size, good stability, and a specific biological function. Due to the specific cleavage of lysozyme to PGN, a very simple specific and sensitive detection method for lysozyme was developed based on the PRLS signal of PGN-AuNPs after mixing with lysozyme for 1.5 h. The enhanced PRLS signals (ΔIPRLS, at 560 nm) increased linearly with increasing lysozyme in the range 5 nM to 1600 nM with the detection limit down to 2.32 nM (ΔIPRLS = 41.6397 + 0.5332c, R = 0.9961). When the PGN-AuNP based method was applied to assay lysozyme in authentic human serum samples, the recovery efficiency was 106.76-119.32% with the relative standard deviations in the range of 0.14-3.11%, showing good feasibility. The PGN-AuNP based method for lysozyme assay developed here is simple, rapid, selective, and sensitive, which is expected to provide a feasible new method for the diagnosis or prognosis of lysozyme-related diseases in a clinical setting.

New application of the commercial sweetener rebaudioside a as a hepatoprotective candidate: Induction of the Nrf2 signaling pathway.

A large population of drug candidates have failed "from bench to bed" due to unwanted toxicities. We intend to develop an alternative approach for drug discovery, that is, to seek candidates from "safe" compounds. Rebaudioside A (Reb-A) is an approved commercial sweetener from Stevia rebaudiana Bertoni. We found that Reb-A protects against carbon tetrachloride (CCl4)-induced oxidative injury in human liver hepatocellular carcinoma (HepG2) cells. Reb-A showed antioxidant activity on reducing cellular reactive oxygen species and malondialdehyde levels while increasing glutathione levels and superoxide dismutase and catalase activities. Reb-A treatment induced nuclear factor erythroid-derived 2-like 2 (Nrf2) activation and antioxidant response element activity, as well as the expression of heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Further mechanistic studies indicated that c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), mitogen-active protein kinase (MAPK) and protein kinase C epsilon (PKCε) signaling was upregulated. Thus, the present in vitro study conclusively demonstrated that Reb-A is an activator of Nrf2 and is a potential candidate hepatoprotective agent. More importantly, the present study illustrated that seeking drug candidates from "safe" compounds is a promising strategy.

Dual-Recognition Förster Resonance Energy Transfer Based Platform for One-Step Sensitive Detection of Pathogenic Bacteria Using Fluorescent Vancomycin-Gold Nanoclusters and Aptamer-Gold Nanoparticles.

The effective monitoring, identification, and quantification of pathogenic bacteria is essential for addressing serious public health issues. In this study, we present a universal and facile one-step strategy for sensitive and selective detection of pathogenic bacteria using a dual-molecular affinity-based Förster (fluorescence) resonance energy transfer (FRET) platform based on the recognition of bacterial cell walls by antibiotic and aptamer molecules, respectively. As a proof of concept, Vancomycin (Van) and a nucleic acid aptamer were employed in a model dual-recognition scheme for detecting Staphylococcus aureus (Staph. aureus). Within 30 min, by using Van-functionalized gold nanoclusters and aptamer-modified gold nanoparticles as the energy donor and acceptor, respectively, the FRET signal shows a linear variation with the concentration of Staph. aureus in the range from 20 to 108 cfu/mL with a detection limit of 10 cfu/mL. Other nontarget bacteria showed negative results, demonstrating the good specificity of the approach. When employed to assay Staph. aureus in real samples, the dual-recognition FRET strategy showed recoveries from 99.00% to the 109.75% with relative standard derivations (RSDs) less than 4%. This establishes a universal detection platform for sensitive, specific, and simple pathogenic bacteria detection, which could have great impact in the fields of food/public safety monitoring and infectious disease diagnosis.

Antibiotics mediated facile one-pot synthesis of gold nanoclusters as fluorescent sensor for ferric ions.

In this paper, the cheap, easily obtained small antibiotic molecule of vancomycin was employed as reducer/stabilizer for facile one-pot synthesis of water exhibited a bluish fluorescence emission at 410nm within a short synthesis time about 50min. Based on the strong fluorescence quenching due to electron transfer mechanism by the introduction of ferric ions(Fe3+), the Van-AuNCs were interestingly designed for sensitive and selective detecting Fe3+ with a limit of 1.4µmol L-1 in the linear range of 2-100µmol L-1 within 20min. The Van-AuNCs based method was successfully applied to determine Fe3+ in tap water, lake water, river water and sea water samples with the quantitative spike recoveries from 97.50-111.14% with low relative standard deviations ranging from 0.49-1.87%, indicating the potential application of this Van-AuNCs based fluorescent sensor for environmental sample analysis.