Self-Responsive Fluorescence Aptasensor for Lactoferrin Determination in Dairy Products.

In this study, a self-responsive fluorescence aptasensor was established for the determination of lactoferrin (Lf) in dairy products. Herein, the aptamer itself functions as both a recognition element that specifically binds to Lf and a fluorescent signal reporter in conjunction with fluorescent moiety. In the presence of Lf, the aptamer preferentially binds to Lf due to its specific and high-affinity recognition by folding into a self-assembled and three-dimensional spatial structure. Meanwhile, its reduced spatial distance in the aptamer-Lf complex induces a FRET phenomenon based on the quenching of 6-FAM by amino acids in the Lf protein, resulting in a turn-off of the fluorescence of the system. As a result, the Lf concentration can be determined straightforwardly corresponding to the change in the self-responsive fluorescence signal. Under the optimized conditions, good linearities (R2 > 0.99) were achieved in an Lf concentration range of 2~10 µg/mL for both standard solutions and the spiked matrix, as well as with the desirable detection limits of 0.68 µg/mL and 0.46 µg/mL, respectively. Moreover, the fluorescence aptasensor exhibited reliable recoveries (89.5-104.3%) in terms of detecting Lf in three commercial samples, which is comparable to the accuracy of the HPCE method. The fluorescence aptasensor offers a user-friendly, cost-efficient, and promising sensor platform for point-of-need detection.

Simultaneous detection of dual microRNAs related to EV71 using ICP-MS based on metal nanoparticle labeling with hybridization chain reaction.

BACKGROUND: Hand, foot, and mouth (HMFD) disease caused by enterovirus 71 (EV 71), is closely associated with severe clinical manifestations and can be deadly. Early detection of EV 71 can be achieved by detecting the increment in miR296 and miR16 in the serum. Using HCR to amplify signals and convert biological signals into metal nanoparticle signals detectable by ICP-MS is a detection method that can collect more accurate and reliable information, compared with traditional methods, in the detection of biological samples. RESULTS: We described a strategy for the simultaneous detection of miR296 and miR16 by ICP-MS based on metal nanoparticles (NPs) labeling with HCR. Briefly, single-stranded DNA (ssDNA) and magnetic beads (MBs), as well as NPs and signal probes for miRNA (Sp-miR) were firstly conjugated via the streptavidin-biotin recognition system, constituting ssDNA-MBs and NPs-Sp-miR complex, respectively. The latter complex then hybridized with the former through HCR, generating the nanosensors for targets. Then, the targets were added and hybridized with ssDNA, and the HCR complex with NPs was released into the solution. Finally, the corresponding signals of the NPs were measured by ICP-MS. Results demonstrated that the developed method had good sensitivity and satisfactory selectivity and precision. Furthermore, when applied to biological samples with a complex matrix, the developed method also showed good recovery (88 % - 92 %) and reproducibility (RSD<10 %). SIGNIFICANCE: This method contributes to the early diagnosis of HFMD and opens up ideas for the further development of high-throughput biomarker detection. The strategy has practical potential for miR296 and miR16 detection in biological samples and provides a promising tool for multiple miRNA detection.

Heavy metals in meat products from Shandong, China and risk assessment.

In this study 13 heavy metals were analysed in representative livestock meat, poultry meat, livestock offal and poultry offal samples (20 per category) from marketplaces and retail stores in 16 cities in Shandong province, China. The investigated heavy metals were Cu, Cr, V, Ni, As, Se, Sn, Cd, Pb, Sb, Mn, Ba and Hg. Results revealed mean levels of total heavy metals in meat and offal of 1.56 mg/kg and 39.8 mg/kg, respectively. Cu, Cr, Mn, Ni, Se, Ba and Pb were found in all samples (100%), followed by Hg (95.0%), V (91.3%), Sn (73.8%), Cd (51.3%), As (21.3%) and Sb (11.3%). Hazard Quotient (HQ) and Hazard Index (HI) values showed that high meat intake can cause potential health risks. Thus, continuous monitoring of health risks and trends of heavy metals in meat products is needed, both for food safety and consumer's health.

ICP-MS and fluorescence dual-mode detection of ZIKV-RNA based on quantum dot labeling with hybridization chain reaction.

The detection of Zika virus (ZIKV) is of great significance to human life and health. Herein, we presented an ICP-MS and fluorescent dual-mode sensor for quantitative analysis of Zika virus RNA fragments (ZIKV-RNA), which employed quantum dots (QDs) as signal tags and combined with hybridization chain reaction (HCR). The dual-mode sensor realized cross-checking of the analysis results and improved the assay accuracy. Firstly, the single-stranded DNA (ssDNA) was anchored on the surface of magnetic beads (MBs). Afterward, HCR was conducted with probe DNA-CdSe quantum dots conjugates (pDNA-QDs) and link DNA (lDNA), producing the MBs-ssDNA-[pDNA-QDs-lDNA]n conjugates. In the presence of target ZIKV-RNA, a strand displacement reaction occurred, leading to the dissociation of the [pDNA-QDs-lDNA]n labels from the conjugates into the solution. Finally, the signal intensity was detected using ICP-MS and fluorescence analysis, with achieved limits of detection of 131 pM and 152 pM, respectively. The inter-assay RSD values of fluorescence and ICP-MS were 3.94 % and 4.26 % at 10 nM level, respectively, showing that the method had good precision. This method showed high selectivity and was applied to the analysis of biological fluids. There was no significant difference between the results of ICP-MS modes and fluorescence mode. This method offers a new strategy for sensitivity analysis of ZIKV-RNA and exhibits promise in clinical applications for diagnosis.

Legacy per- and polyfluoroalkyl substances (PFASs) especially alternative PFASs in shellfish from Shandong Province, China: Distribution, sources, and health risk.

We investigated the distribution of 8 per- and polyfluoroalkyl substances (PFASs) in 321 shellfish samples collected from four coastal cities along the Yellow Sea and Bohai Sea of Shandong Province, China. The concentrations of total PFASs (∑PFASs) were in the range of 0.061-178.259 ng/g wet weight (ww). Two legacy long-chain compounds were dominant. Three emerging compounds and two short-chain alternatives were also observed with higher concentration and detection frequency than in previous studies, whereas 4, 8-dioxa-3H-perfluorononanoate acid (ADONA) was not detected. There were differences in concentrations and composition profiles of PFASs among different species, as well as among different sampling cities. According to scores of principal component analysis, metal plating plants, textile treatments, and fluoropolymer products were considered as the main sources of PFAS contamination in shellfish. Furthermore, a potential health risk of perfluorooctanoic acid should be highly considered for local residents that frequently consume crabs and molluscs.

5-Methyltetrahydrofolate Alleviates Memory Impairment in a Rat Model of Alzheimer's Disease Induced by D-Galactose and Aluminum Chloride.

The effects of 5-methyltetrahydrofolate (5-MTHF) on a rat model of Alzheimer's disease (AD) induced by D-galactose (D-gal) and aluminum chloride (AlCl3) were investigated. Wistar rats were given an i.p. injection of 60 mg/kg D-gal and 10 mg/kg AlCl3 to induce AD and three doses of 1 mg/kg, 5 mg/kg or 10 mg/kg 5-MTHF by oral gavage. A positive control group was treated with 1 mg/kg donepezil by gavage. Morris water maze performance showed that 5 and 10 mg/kg 5-MTHF significantly decreased escape latency and increased the number of platform crossings and time spent in the target quadrant for AD rats. The administration of 10 mg/kg 5-MTHF decreased the brain content of amyloid ß-protein 1-42 (Aß1-42) and phosphorylated Tau protein (p-Tau) and decreased acetylcholinesterase and nitric oxide synthase activities. Superoxide dismutase activity, vascular endothelial growth factor level and glutamate concentration were increased, and malondialdehyde, endothelin-1, interleukin-6, tumor necrosis factor-alpha and nitric oxide decreased. The administration of 10 mg/kg 5-MTHF also increased the expression of disintegrin and metallopeptidase domain 10 mRNA and decreased the expression of ß-site amyloid precursor protein cleavage enzyme 1 mRNA. In summary, 5-MTHF alleviates memory impairment in a D-gal- and AlCl3-exposed rat model of AD. The inhibition of Aß1-42 and p-Tau release, reduced oxidative stress, the regulation of amyloid precursor protein processing and the release of excitatory amino acids and cytokines may be responsible.

Highly sensitive detection of dopamine based on gold nanoflowers enhanced-Tb(III) fluorescence.

We developed a trace level detection method for dopamine (DA) based on the metal-enhanced fluorescence (MEF) effect of gold nanoflowers (AuNFs). AuNFs prepared were excellent enhancement fluorescence substrates due to their unique morphology with rich edges and sharp quoins. DA was the target analyte and also as a bridge reagent that could regulate the distance between AuNFs and Tb3+. The characteristic fluorescence of Tb3+ was enhanced significantly through the synergistic effect between the luminescence sensitized by DA and the MEF caused by AuNFs. Under the optimum experimental conditions, the fluorescence intensity of Tb3+ at 545 nm demonstrated very significant sensing ability against DA concentration and showed a good linear relationship in the range of 0.80-300 nM and the limit of detection was 0.21 nM (S/N = 3). The proposed method was also validated in serum samples and the dopamine hydrochloride injection samples with satisfactory results.

Investigation into the Properties of L-5-Methyltetrahydrofolate and Seal Oil as a Potential Atherosclerosis Intervention in Rats.

Atherosclerosis is a chronic inflammatory disease that leads to tissue ischemia. As the biologically active form of folic acid, L-5-methyltetrahydrofolate (L-5-MTHF) can improve endothelial function. And Seal oil plays a beneficial role in the progression of atherosclerosis. The study aims to evaluate beneficial effects of L-5-MTHF alone or in combination with Seal oil on atherosclerosis. Seventy-two male Wistar rats were randomly divided into 6 groups: control (normal diet), atherosclerosis (high-fat diet), folic acid (high-fat+3 mg/kg folic acid), low-dose L-5-MTHF (high-fat+3 mg/kg L-5-MTHF), low-dose L-5-MTHF+Seal oil (high-fat+3 mg/kg L-5-MTHF+0.5 g/kg Seal oil), high-dose L-5-MTHF (high-fat+10 mg/kg L-5-MTHF). After 13 wk, rats were sacrificed. Rats exhibiting atherosclerosis had dyslipidemia and serious aortic lesions. Supplementation with low-dose L-5-MTHF+Seal oil or use of high-dose L-5-MTHF increased serum folate concentrations, decreased homocysteine levels, improved the serum lipid profile, up-regulated expression of NO and NOS, enhancement of the antioxidant properties of GSH-Px activity and reduction in the concentration of MDA, levels of Olr1 and RelA mRNA decreased in aortic tissues, and expression of inflammatory factors, TNF-α, IL-6, IL-1ß and endothelial cell injury factors ET-1 and sICAM-1, were also down-regulated. In addition, HD-L-5-MTHF increased the antioxidant activity of serum SOD. We conclude that L-5-MTHF has obvious anti-inflammatory and antioxidant effects on diseased blood vessels. The intervention of L-5-MTHF alone or in combination with Seal oil can improve atherosclerosis in rats and reduce the occurrence of aortic lesions. The anti-atherosclerotic mechanism may be related to down-regulation of Olr1 and RelA expression.

Cross-sectional study: Relationship between serum trace elements and hypertension.

BACKGROUND: A balanced intake of trace elements is beneficial for chronic diseases such as hypertension. However, the available information regarding trace elements that may be independently associated with hypertension is limited, and the relationship between this disorder and element ratios also remains unclear. METHODS: A total of 6,754 subjects from rural China were selected, after exclusion of patients who were under 18, had incomplete data or had additional related disorders, by multi-stage simple random and cluster sampling (participation rate: 95.22 %). Subjects were divided into a hypertensive (H) and a control (C) group. Data were collected on blood pressure and 12 serum trace elements were measured by flame atomic absorption spectrometry and inductively coupled plasma-mass spectrometry. Other basic information was collated from questionnaires and biochemical indicators were measured via kits. RESULTS: Differences in serum levels of magnesium (Mg(mg/l): H: 27.43 ± 12.72; C: 26.33 ± 12.16), iron (Fe(mg/l): H: 1.99 ± 1.24; C: 1.84 ± 1.16), copper (Cu(mg/l): H: 1.19 ± 0.37; C: 1.10 ± 0.36), boron (B(µg/l): H: 50.00 ± 25.21; C: 47.57 ± 26.25), selenium (Se(µg/l): H: 125.12 ± 32.81; C: 118.80 ± 29.72) and chromium (Cr(µg/l): H: 8.77 ± 10.12; C: 10.12 ± 10.72) between the hypertensive and control groups were found. There were no differences in serum contents of calcium (Ca(mg/l): H: 112.43 ± 58.25; C: 111.00 ± 59.49), zinc (Zn(mg/l): H: 1.50 ± 1.97; C: 1.44 ± 1.88), arsenic (As(µg/l): H: 4.17 ± 3.94; C: 4.10 ± 4.00), manganese (Mn(µg/l): H: 4.15 ± 4.03; C: 4.07 ± 4.05), cadmium (Cd(µg/l): H: 1.14 ± 1.11; C: 1.18 ± 1.12) or lead (Pb(µg/l): H: 4.22 ± 8.90; C: 4.26 ± 10.25). The serum Cr and Cd concentrations of hypertensive men were lower than that of male controls while Mg, Cu, Ca and Se concentrations in male controls were lower. Further differences were apparent and Fe, B, Se, Mg and Cu all showed higher levels in hypertensive females whereas Cr concentrations were higher in female controls. Serum Zn and B levels showed age-related variations among hypertensive patients and concentrations of serum Cu, Zn, Se and B showed age-related variations among control subjects. For hypertensive patients, the odds ratio (OR) and 95 % confidence interval (CI) for the association of serum Cu, Se and Cr levels with hypertension were Cu: 1.36 (1.12-1.66); Se: 1.03 (1.01-1.05); Cr: 0.89 (0.83-0.96). Moreover, when the participants in the grouping with the highest copper/zinc (Cu/Zn) and magnesium/manganese (Mg/Mn) ratios were compared with the reference group, the OR and 95 % CI for hypertension were 1.22 (1.04-1.44) and 1.20 (1.01-1.42), respectively. CONCLUSIONS: Levels of serum trace elements showed age- and sex-related differences in a group of rural Chinese adults with hypertension and healthy participants. Serum concentrations of Cu, Se and Cr may be independently associated with hypertension. Higher serum ratios of Cu:Zn and Mg:Mn may also be associated with hypertension. Further randomized trials are necessary to elucidate the true relationship between levels of Cu, Se, Cr, Cu:Zn, Mg:Mn and hypertension.

Occurrence and dietary exposure of heavy metals in marketed vegetables and fruits of Shandong Province, China.

The contamination of heavy metals in vegetables and fruits is a serious threat to food safety and human health. The present study was designed to investigate the occurrence and dietary exposure of lead (Pb), arsenic (As), cadmium (Cd), and mercury (Hg) in vegetables and fruits in Shandong Province, China. Results demonstrated that the mean level of total heavy metals was 30.25 µg/kg. The most frequently found heavy metal was Cd (69.2%) with a mean value of 11.54 µg/kg. The mean exposure values of Pb, As, Cd, and Hg in vegetables were 0.052, 0.045, 0.038, and 2.40 × 10-3 µg/kg bw/day, respectively. Moreover, the calculated hazard quotient (HQ) values of mean levels for these four heavy metals were all less than 1, indicating the health risk of heavy metal exposure caused by vegetable consumption was low. This study has displayed baseline information on heavy metal contamination in vegetables and fruits, which can provide useful data support for the formulation of relevant standards and government management.

Cell membrane covered polydopamine nanoparticles with two-photon absorption for precise photothermal therapy of cancer.

HYPOTHESIS: In view of the photothermal effect of polydopamine (PDA) nanoparticles and their internal D-π-D structures during assembly, the two-photon excited properties of PDA were studied toward the biomedical application. Further, the PDA molecules were coordinated with Mn2+ and the assembled nanoparticles were covered by cancer cell membranes, the complex system could be used directly for the treatment of cancer with photothermal and chemodynamic therapy. EXPERIMENTS: The two-photon excited PDA-Mn2+ nanoparticles were used for the photothermal therapy combined with chemodynamic therapy. The complexes were coated with cancer cell membranes in order to enhance the tumor homologous efficiency. Multi-modal bioimaging and anti-tumor detections were carried out both in vitro and in vivo. FINDINGS: PDA nanoparticles were demonstrated to have both good two-photon excited fluorescence and photothermal efficiency. The assembled nanoparticles modified with Mn2+ and cancer cell membranes have an obvious targeting and synergetic anti-cancer efficiency. The system creates a simple way for a precise operation with multi-modal imaging function.

Stable 5-GHz fundamental repetition rate passively SESAM mode-locked Er-doped silica fiber lasers.

A stable passively mode-locked Er-doped silica fiber laser with a fundamental repetition rate of up to 5 GHz is demonstrated, which, to the best of our knowledge, is the highest repetition rate for 1.5 µm semiconductor saturable absorber mirror (SESAM) mode-locked Er-doped silica fiber (EDF) lasers. A segment of commercially available EDF with a net gain coefficient of 1 dB/cm is employed as gain medium. The compact Fabry-Pérot (FP) cavity features a fiber mirror, namely multiple-layer dielectric films (DFs) directly coated on end facet of a passive fiber ferrule, enabling a short cavity length of 2 cm configured. The mode-locked oscillator operates at 1561.0 nm with a signal-to-noise ratio (SNR) of 62.1 dB, whose average power is boosted to 27 mW by a single-mode Er-doped fiber amplifier (EDFA) and spectral bandwidth is broadened form 0.69 nm to 1.16 nm with a pulse width of 3.86 ps. The fiber laser shows excellent spectral stability without conspicuous wavelength drifting for 3 hours. Moreover, the basic guidelines of selecting SESAM for high repetition rate passively mode-locked fiber lasers is given.

Two-photon excited peptide nanodrugs for precise photodynamic therapy.

A novel peptide nanodrug composed of three functional motifs, bis(pyrene), FFVLK and CREKA, was used as a two-photon excited photosensitizer for precise photodynamic therapy (PDT). The system presented excellent two-photon imaging ability, tumor target effect and high reactive oxygen species productivity for improving treatment precision and efficiency in PDT.

Occurrence of polycyclic aromatic hydrocarbons in fried and grilled fish from Shandong China and health risk assessment.

Diet is the main way for the human body to ingest polycyclic aromatic hydrocarbons (PAHs). In this study, the occurrence, dietary exposure, and health risks of 15 PAHs in 31 fried and grilled fish samples were investigated, which were collected from the Shandong Province of China. The results showed that benzo[a]pyrene (BaP) of 5 samples exceeded the European Union (EU) limit value. Naphthalene (NaP) and fluorene (Fle) were present in all samples, and the average concentration of ∑15PAHs was 91.1 µg/kg, with light PAHs dominated. The average contamination level of ∑15PAHs in fried and grilled fish was distributed differently, and there seemed to be more PAH contamination in the grilled samples. The results of the margin of exposure (MOE) suggested that PAH ingestion through fried and grilled fish did not imply significant toxicological concern for consumers in Shandong. The incremental lifetime cancer risk (ILCR) values for the consumption of fried and grilled fish were higher than 1 × 10-6, indicating a potential health risk in the adult population. The study provides baseline health information on PAH intake by residents due to dietary exposure to fried and grilled fish food products, suggesting that health risk monitoring of PAHs in such foods should be continually performed.

Pt@polydopamine nanoparticles as nanozymes for enhanced photodynamic and photothermal therapy.

Polydopamine nanoparticles were used to stabilize a nano-Pt catalyst to relieve tumour hypoxia in photodynamic therapy (PDT). Polydopamine not only provides a platform for carrying nano-Pt and photosensitizers but is also used as a photothermal reagent for photothermal therapy (PTT). The system presented an enhanced anti-tumor therapy effect through a combined PDT and PTT mechanism.

Linearly polarized single-frequency fiber laser based on the Yb:YAG-crystal derived silica fiber.

A linearly polarized low-noise single-frequency fiber laser was demonstrated by using a homemade 1.2-cm-long Yb:YAG crystal derived silica fiber. A maximum output power of greater than 60 mW was obtained with a signal-to-noise ratio of ∼80dB and a polarization extinction ratio of 27.8 dB. Additionally, the relative intensity noise was measured to be -145dB/Hz above 6.5 MHz. A frequency fluctuation of less than 20 MHz was also obtained. The output power was scaled up to 14.5 W with a one-stage all-fiber amplifier scheme with a slope efficiency of 56.4%.

Phocea, Pseudoflavonifractor and Lactobacillus intestinalis: Three Potential Biomarkers of Gut Microbiota That Affect Progression and Complications of Obesity-Induced Type 2 Diabetes Mellitus.

PURPOSE: The purpose of this study was to explore the difference and association between intestinal microbiota and plasma metabolomics between type 2 diabetes mellitus (T2DM) and normal group and to identify potential microbiota biomarkers that contribute the most to the difference in metabolites. METHODS: Six male ZDF model (fa/fa) rats were fed by a Purina #5008 Lab Diet (crude protein 23.5%, crude fat 6.5%) for 3 weeks and their age-matched 6 ZDF control (fa/+) rats were fed by normal rodent diet. Their stool and blood samples were collected at 12 weeks. To analyze the microbial populations in these samples, we used a 16S rRNA gene sequencing approach. Liquid chromatography-mass spectrometry (LC-MS) followed by multivariate statistical analysis was applied to the plasma metabolites profiling. Correlation analysis of them was calculated by Pearson statistical method. RESULTS: Twelve potential biomarkers of intestinal microbial flora and 357 differential metabolites were found in ZDF fa/fa rats, among which there are three flora that contributed the most to the perturbation of metabolites, including genus Phocea, Pseudoflavonifractor and species Lactobacillus intestinalis. CONCLUSION: Our study demonstrates the alterations of the abundance and diversity of the intestinal microbiota and the perturbation of metabolites in ZDF rats (fa/fa). We found three potential biomarkers of intestinal microbiota that may lead to perturbation in plasma metabolites. This may prompt new pathogenesis of obesity-related T2DM, but we also need to study further about the causal relationship between intestinal microbe and T2DM, so as to find the target of T2DM treatment or preventive measures.

110 mW single-frequency Yb:YAG crystal-derived silica fiber laser at 1064 nm.

A single-frequency laser based on Yb:YAG crystal-derived silica fiber (YDSF) was demonstrated. The YDSF was fabricated by a molten-core method with a doping concentration of 4.8 wt. % for Yb2O3, whose gain coefficient and transmission loss were measured to be 1.7 dB/cm and 0.005 dB/cm, respectively. An over 110 mW stable single-frequency laser at 1064 nm was obtained based on a distributed Bragg reflector setup, showing a slope efficiency of 18.5%. The signal-to-noise ratio was ∼80 dB, and the frequency fluctuation was less than 20 MHz within 10 min.

All-fiber-integrated Yb:YAG-derived silica fiber laser generating 6 W output power.

A Yb:YAG-derived silica fiber was fabricated by a molten-core fabrication method, in which a Yb:YAG crystal was used as the core material and a silica tube was used as the cladding material. The fiber's transmission loss was measured to be 0.49 dB/m at 1.55 µm, using a cut-back method. The fiber microstructure image showed that the cladding region was a uniform glass structure, while the core structure was amorphous. An all-fiber-integrated cladding-pumped laser based on Yb:YAG-derived silica fiber was demonstrated. With an incident pump power of 28 W, an output power of 6 W was obtained at 1.06 µm, with a slope efficiency of 21.7%.

Cross-sectional Study: Relationship Between Serum Selenium and Hypertension in the Shandong Province of China.

Although selenium, which is a necessary trace element for the human body, has been considered to be beneficial to the cardiovascular system and helpful to lower blood pressure, more and more evidence shows that high amounts of selenium are a risk factor for hypertension. A random multistage sampling which included the cluster method was performed; a total of 9076 urban and rural residents between 18 and 80 years old in the Shandong province of China were investigated by questionnaire, physical examination, and laboratory tests. The prevalence of hypertension was 42.1% in males and 35.3% in females. The mean (standard deviation) selenium concentration was 124.68 (36.32) µg/l in males and 119.54 (31.88) µg/l in females. After adjusting for potential confounders, logistic regression analysis showed that the highest selenium levels were associated with a risk of hypertension (OR = 1.192; 95% CI 1.009-1.407) in females, while there was no significant difference in males (OR = 1.043; 95% CI 0.864-1.259). Our findings suggest that high selenium levels in females are more likely to increase the risk of hypertension compared to similar levels in males. More attention should be paid to the metabolic mechanisms and physiological effects of selenium in females.