In Situ Electrospinning MOF-Derived Highly Dispersed α-Cobalt Confined in Nitrogen-Doped Carbon Nanofibers Nanozyme for Biomolecule Monitoring.

Designing a metal-organic framework (MOF)-derived nanozyme with highly dispersed active sites and high catalytic activity as well as robust structure for colorimetric biosensing of diverse biomolecules remains a substantial challenge. Here, an MOF-derived highly dispersed and pure α-cobalt confined in a nitrogen-doped carbon nanofiber (α-Co@NCNF) nanozyme with superior glucose oxidase (GOD)- and peroxidase (POD)-like activities was constructed for colorimetric assay of multiple biomolecules. Specifically, the α-Co@NCNF nanozyme was synthesized, utilizing in situ electrospinning Co-MOFs into polyacrylonitrile nanofiber (PAN) followed by a pyrolysis process. Taking advantage of the in situ electrospinning strategy, the α-Co nanoparticles were confined in continuous porous NCNF to restrict the growth and prevent the aggregation and oxidation during the pyrolysis process. The resulting special structure considerably improved the enzyme-like performance. A series of experiments validate that the enzyme-like activity of the α-Co@NCNF nanozyme was superior to that of Co@CoO@NCNF (derivatives from Co-MOFs grown on the surface of PAN nanofiber) and nature enzymes. Furthermore, α-Co@NCNF nanozyme-based colorimetric biosensing was developed for monitoring glucose, hydrogen peroxide (H2O2), and glutathione (GSH) and the corresponding linear ranges are 0.1-50 and 50-900 µM and 5-55 and 0.1-20 µM accompanied by the corresponding low detection of 0.03, 1.66, and 0.03 µM. The proposed method for the construction of α-Co@NCNF nanozyme with dual enzyme-like properties provides a new insight for designing novel nanozymes and has prospects for application in colorimetric biosensing.

Structure Remodeling Strategy for Open-Cage NiFe@Fe-bis-PBA with Enhanced Peroxidase-like Activity To Monitor Tumor Markers.

The inherent metal elements and structures of Prussian blue analogue (PBA) nanozymes have restricted their enzyme-mimicking activity. Therefore, the rational regulation of PBA nanozymes to improve their catalytic activity is highly desirable for biosensing applications. Herein, we propose a structure remodeling strategy to construct an open-cage Fe PBA-anchored NiFePBA (NiFe@Fe bis-PBA) nanozyme with significantly enhanced enzyme-mimicking activity. The formation process and mechanism for this bis-PBA nanozyme were studied in detail. Specifically, a cubic NiFePBA precursor was first synthesized and modified with polyvinylpyrrolidone (PVP). With the aid of hydrochloric acid, the added potassium ferricyanide was reduced by PVP and re-coordinated on the surface of NiFePBA to form the NiFe@Fe bis-PBA nanozyme with a special open-cage core-shell structure. The resultant NiFe@Fe bis-PBA nanozyme was further exploited to immobilize secondary antibodies, serving as a novel signal probe for developing highly sensitive electrochemical immunosensors for monitoring tumor markers. The constructed electrochemical immunosensor possesses a very wide linear range of 0.005-100 ng/mL and a low detection limit of 0.89 pg/mL for alpha-fetoprotein with high specificity and acceptable reproducibility and stability. This work offers a general and promising strategy for remodeling PBA nanozymes with a very favorable structure and metal element distribution, which enhances their enzyme-mimicking properties for applications in different fields.

The protective effect and mechanism of glycosides of cistanche deserticola on rats in middle cerebral artery occlusion (MCAO) model.

Cerebral ischemia-reperfusion injury (CIRI) occurs frequently clinically as a complication following cardiovascular resuscitation resulting in neuronal damage specifically to the hippocampal CA1 region with consequent cognitive impairment. Apoptosis and oxidative stress were proposed as major risk factors associated with CIRI development. Previously, glycosides obtained from Cistanche deserticola (CGs) were shown to play a key role in counteracting CIRI; however, the underlying mechanisms remain to be determined. This study aimed to investigate the neuroprotective effect of CGs on subsequent CIRI in rats. The model of CIRI was established for 2 hr and reperfusion for 24 hr by middle cerebral artery occlusion (MCAO) model. The MCAO rats were used to measure the antioxidant and anti-apoptotic effects of CGs on CIRI. Neurological function was evaluated by the Longa neurological function score test. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to detect the area of cerebral infarction. Nissl staining was employed to observe neuronal morphology. TUNEL staining was used to detect neuronal apoptosis, while Western blot determined protein expression levels of factors for apoptosis-related and PI3K/AKT/Nrf2 signaling pathway. Data demonstrated that CGs treatment improved behavioral performance, brain injury, and enhanced antioxidant and anti-apoptosis in CIRI rats. In addition, CGs induced activation of PI3K/AKT/Nrf2 signaling pathway accompanied by inhibition of the expression of apoptosis-related factors. Evidence indicates that CGs amelioration of CIRI involves activation of the PI3K/AKT/Nrf2 signaling pathway associated with increased cellular viability suggesting these glycosides may be considered as an alternative compound for CIRI treatment.

Effect of total flavonoids of Dracocephalum moldavica L. On neuroinflammation in Alzheimer's disease model amyloid-ß (Aß1-42)-peptide-induced astrocyte activation.

One of the main pathological features noted in Alzheimer's disease (AD) is the presence of plagues of aggregated ß-amyloid (Aß1-42)-peptides. Excess deposition of amyloid-ß oligomers (AßO) are known to promote neuroinflammation. Sequentially, following neuroinflammation astrocytes become activated with cellular characteristics to initiate activated astrocytes. The purpose of this study was to determine whether total flavonoids derived from Dracocephalum moldavica L. (TFDM) inhibited Aß1-42-induced damage attributed to activated C8-D1A astrocytes. Western blotting and ELISA were used to determine the expression of glial fibrillary acidic protein (GFAP), and complement C3 to establish the activation status of astrocytes following induction from exposure to Aß1-42. Data demonstrated that stimulation of C8-D1A astrocytes by treatment with 40 µM Aß1-42 for 24 hr produced significant elevation in protein expression and protein levels of acidic protein (GFAP) and complement C3 accompanied by increased expression and levels of inflammatory cytokines. Treatment with TFDM or the clinically employed drug donepezil in AD therapy reduced production of inflammatory cytokines, and toxicity initiated following activation of C8-D1A astrocytes following exposure to Aß1-42. Therefore, TFDM similar to donepezil inhibited inflammatory secretion in reactive astrocytes, suggesting that TFDM may be considered as a potential compound to be utilized in AD therapy.

Cannabidiol improves the cognitive function of SAMP8 AD model mice involving the microbiota-gut-brain axis.

Cannabidiol (CBD), a natural component extracted from Cannabis sativa L. exerts neuroprotective, antioxidant, and anti-inflammatory effects in Alzheimer's disease (AD), a disease characterized by impaired cognition and accumulation of amyloid-B peptides (Aß). Interactions between the gut and central nervous system (microbiota-gut-brain axis) play a critical role in the pathogenesis of neurodegenerative disorder AD. At present investigations into the mechanisms underlying the neuroprotective action of CBD in AD are not conclusive. The aim of this study was thus to examine the influence of CBD on cognition and involvement of the microbiota-gut-brain axis using a senescence-accelerated mouse prone 8 (SAMP8) model. Data demonstrated that administration of CBD to SAMP8 mice improved cognitive function as evidenced from the Morris water maze test and increased hippocampal activated microglia shift from M1 to M2. In addition, CBD elevated levels of Bacteriodetes associated with a fall in Firmicutes providing morphologically a protective intestinal barrier which subsequently reduced leakage of intestinal toxic metabolites. Further, CBD was found to reduce the levels of hippocampal and colon epithelial cells lipopolysaccharide (LPS), known to be increased in AD leading to impaired gastrointestinal motility, thereby promoting neuroinflammation and subsequent neuronal death. Our findings demonstrated that CBD may be considered a beneficial therapeutic drug to counteract AD-mediated cognitive impairment and restore gut microbial functions associated with the observed neuroprotective mechanisms.

Functional Zonation Strategy of Heterodimer Nanozyme for Multiple Chemiluminescence Imaging Immunoassay.

Although nanozymes with intrinsic enzyme-like characteristics have aroused great interest in the biosensing field, the challenge is to keep high enzyme-like activity of the nanozyme after the modification of biomolecules onto nanozymes. Herein, a functional zonation strategy of a heterodimer nanozyme was proposed to tackle the challenge and further construct a multiple chemiluminescence (CL) imaging immunoassay. Here Fe3O4-Au as a heterodimer nanozyme model was divided into two zones, in which Fe3O4 nanoparticles (NPs) were regarded as a nanozyme zone and AuNPs were defined as an antibody immobilization zone. A signal amplification probe (Fe3O4-Au-Ab2) was prepared by modifying the secondary antibody (Ab2) on AuNPs of the Fe3O4-Au heterodimer owing to the Au-S bond. The exposed Fe3O4 of the Fe3O4-Au-Ab2 probe shows very high peroxidase-like activity and can efficiently catalyze H2O2-luminol to produce strong CL imaging signals for multiple antigens detection. Using chicken interleukin-4 (ChIL-4) and chicken gamma interferon (ChIFN-γ) as models, the proposed CL imaging immunoassay shows wide linear ranges (0.005-0.10 ng/mL for both ChIL-4 and ChIFN-γ) and low detection limits (0.58 pg/mL for ChIL-4, 0.47 pg/mL for ChIFN-γ) with the characteristics of high sensitivity, high specificity, and good stability. This work provides a promising functional zonation concept for nanozymes to construct new types of nanozyme probes for immunoassay of multiple biomolecules.

Urchin-like PtNPs@Bi2S3: synthesis and application in electrochemical biosensor.

Efficient urchin-like Pt nanoparticles@Bi2S3 (PtNPs@Bi2S3) composite materials were prepared by a composite soft template synthesis of urchin-like Bi2S3 and then the microwave-assisted growth of PtNPs onto the Bi2S3 nanostructure. For the first time, an accurate electrochemical glucose biosensor was fabricated via immobilizing glucose oxidase (GOx) on PtNPs@Bi2S3. The PtNPs@Bi2S3 composite was investigated via scanning electron microscopy, electrochemical impedance spectroscopy, Fourier transform infrared spectroscopy, and cyclic voltammetry. The PtNPs@Bi2S3 composite provides a large surface area to load a large number of enzyme molecules, which maintains the biological activity. PtNPs loaded on Bi2S3 enhanced the conductivity and improved the direct electron transfer of the proposed biosensor with the synergistic effect. The fabricated electrochemical biosensor possesses high sensitivity, and a wide linear range from 0.003 mM to 0.1 mM and 0.1 mM to 1.9 mM. Moreover, the biosensor has outstanding stability, superior selectivity and good repeatability, which can be utilized to monitor the glucose level in practical human serum. The PtNPs@Bi2S3 composite supplies a special matrix for immobilizing proteins and potential for establishing other effective biosensors.

Dual-strategy biosensing of glucose based on multifunctional CuWO4 nanoparticles.

In this research, dual-strategy biosensing of glucose was proposed based on multifunctional CuWO4 nanoparticles (CuWO4 NPs), which were prepared for the application of electrochemical and colorimetric sensing of glucose. CuWO4 NPs show large specific surface area and good conductivity as well as excellent peroxidase-like activity. A sensitive and selective electrochemical glucose biosensor was fabricated with the immobilization of glucose oxidase (GOx) on a CuWO4 NP modified electrode for enhancing the direct electron transfer behavior. A wide linear range of 0.005-1.8 mM with a low detection limit of 1.5 µM and a high sensitivity of 28.02 mA M-1 cm-2 were achieved by using the electrochemical biosensor. Meanwhile, a colorimetric and visual glucose biosensor was constructed based on the GOx/CuWO4 cascade nanozyme, which shows a linear range of 0.05-1.0 mM with excellent selectivity. CuWO4 NPs as a promising matrix open up a dual-strategy biosensor for sensitive and selective detection of glucose.

Ultrasensitive multiplex SERS immunoassay based on porous Au-Ag alloy nanoparticle-amplified Raman signal probe and encoded photonic crystal beads.

An ultrasensitive multiplex surface-enhanced Raman scattering (SERS) immunoassay was developed using porous Au-Ag alloy nanoparticles (p-AuAg NPs) as Raman signal amplification probe coupling with encoded photonic crystal microsphere. p-AuAg NPs were synthesized and modified with the second antibody (Ab2) and Raman tag (mercaptobenzoic acid, MBA) to prepare a Raman signal-amplified probe. The high porosity of the p-AuAg NPs enables significant coupling of the localized surface plasmon resonance and thus abundant inherent hotspots for Raman signal enhancement. 3D-ordered silver nanoparticles-coated silica photonic crystal beads (Ag/SPCBs) were prepared as encoded SERS substrate for multiplex detection using their reflection peaks. The signal-amplified probe was used for multiplex detection of tumor markers carcinoembryonic antigen (CEA) and alpha fetoprotein (AFP). The wide linear ranges of 10-7-103 ng/mL for CEA and 10-4-103 ng/mL for AFP with detection limits of 1.22 × 10-8 ng/mL and 2.47 × 10-5 ng/mL for CEA and AFP at a signal-to-noise ratio of 3 were obtained. The proposed multiplex SERS immunoassay method displays ultrahigh sensitivity, wide linear range, and excellent specificity, which can be successfully applied to measure clinical serum samples with satisfactory results. The research provides a novel SERS signal enhancement strategy for the multiplex bioassay.

Facile synthesis of a nanorod-like MoS2 nanostructure for sensitive electrochemical biosensing application.

A novel nanorod-like MoS2 semiconductor nanostructure was synthesized through a simple two-step method. The nanorod-like MoS2 nanostructure was exploited as an electrode material to immobilize enzymes and for electrochemical sensing application. Characterization of the nanorod-like MoS2 nanostructure and the resultant biosensor was performed by scanning electron microscopy, Fourier transform infrared spectroscopy, electrochemical impedance spectroscopy, and cyclic voltammetry. Enzyme molecules loaded at the MoS2 nanostructure retained their native structure and bioactivity. The direct electron transfer of glucose oxidase at the MoS2 nanostructure coated glassy carbon electrode was enhanced greatly. At an optimal potential of -0.45 V, the electrochemical glucose sensor had wide linear ranges of 1.5 × 10-5-3.25 × 10-4 M and 3.25 × 10-4-1.43 × 10-3 M, and a low detection limit of 0.005 mM (S/N = 3) with a high sensitivity of 25.06 ± 0.5 mA M-1 cm-2. At the same time, the present biosensor showed excellent selectivity, reproducibility and stability for glucose. What's more, the biosensor was successfully applied to the determination of practical samples.

N, O-codoped hierarchical porous graphitic carbon for electrochemical immunosensing of Lactobacillus rhamnosus GG.

An ultrasensitive label-free electrochemical immunosensor was fabricated for quantitative detection of Lactobacillus rhamnosus GG (LGG). The N/O co-doped three-dimensional hierarchical porous graphitic (THPG) carbon was synthesized by a one-step synthesis of polyaniline hydrogel, and followed by simple carbonization and chemical activation procedures. Because of the unique structure design, the obtained THPG carbon networks possess an ultra-large specific surface area of 4859 m2 g-1 along with a class of highly graphitic carbons. The results offer an enormous surface area and excellent electrical conductivity for label-free electrochemical immunosensing of probiotic L. rhamnosus strain. Under optimal conditions, the immunosensor showed a good linear relationship between peak current and concentration of LGG (R2 = 0.9976), with a detection limit of 2 CFU mL-1. Furthermore, this label-free immunosensor also shows good specificity, long-term stability, and reliability, and could be applied to detect probiotic LGG in dairy products and drinks with satisfactory results. The present protocol was shown to be quite promising for practical screening and functional evaluation of probiotic products containing LGG. A ultrasensitive label-free electrochemical immunosensor based on THPG carbon was fabricated for detection of Lactobacillus rhamnosus GG.

Anthocyanins: Promising Natural Products with Diverse Pharmacological Activities.

Anthocyanins are natural products that give color to plants. As natural plant pigments, anthocyanins also have a series of health-promoting benefits. Many researchers have proved that anthocyanins have therapeutic effects on diseases, such as circulatory, nervous, endocrine, digestive, sensory, urinary and immune systems. Additionally, a large number of studies have reported that anthocyanins have an anticancer effect through a wide range of anti-inflammatory and antioxidant effects. The anti-disease impact and mechanism of anthocyanins are diverse, so they have high research value. This review summarizes the research progress of anthocyanins on the pharmacological agents of different diseases to provide references for subsequent research.

Superparamagnetic Nanostructures for Split-Type and Competitive-Mode Photoelectrochemical Aptasensing.

Photoelectrochemical sensing has developed rapidly in the past decade because of its inherent advantages of economic devices and low background noise. However, traditional assembly of photoelectric beacons, probes, and targets on the ITO electrode solid-liquid interface inevitably leads to time-consuming, limited selectivity, poor stability, and nonreproducibility. To overcome these drawbacks, in this work, a unique split-type PEC aptasensor for carcinoembryonic antigen (CEA) was developed in virtue of the sandwich-like structure comprised of magnetic-optical Fe3O4@SiO2@CdS-DNA1, CEA aptamer, and signal element SiO2-Au-DNA2. The sandwich-like structure is easily formed in the liquid phase and can be triggered by competition from low-abundance CEA, resulting in dissociation. By further photocurrent measurement in pure phosphate buffer saline (PBS), coexisting species can be effectively removed from the modified electrode, improving selectivity, stability, and repeatability. These advantages benefit from the preparation of uniform and monodispersed Fe3O4@SiO2@CdS and SiO2-Au particles, DNAs assembly, and an elegant design. Additionally, the as-designed signal-on PEC aptasensor is highly sensitive, short time-consuming, and economical, enabling the detection of CEA in serum specimens. It not only provides an alternative to CEA immunosensors, but also paves the way for high-performance PEC aptasensors.

Synthesis of a manganese dioxide nanorod-anchored graphene oxide composite for highly sensitive electrochemical sensing of dopamine.

In this research, a novel manganese dioxide nanorod-anchored graphene oxide (MnO2 NRs/GO) composite was synthesized by a simple hydrothermal method for electrochemical sensing application. A highly sensitive electrochemical sensor for dopamine (DA) was constructed by modifying glassy carbon electrode (GCE) with MnO2 NRs/GO. The morphology and performance of the composite material and modified GCEs were investigated by using scanning electron microscopy (SEM), X-ray diffraction (XRD) and cyclic voltammetry (CV), respectively. The resultant MnO2 NRs/GO composite has a large electroactive area and shows excellent electrochemical activity toward DA. Under the optimal conditions, the DA sensor shows a linear response in the DA concentration ranges of 0.1 µM-0.08 mM and 0.08-0.41 mM with a low detection limit of 0.027 µM and a high sensitivity of 602.4 µA·mM-1·cm-2. The MnO2 NRs/GO composite provides a promising platform for the construction of a highly sensitive and selective sensor of DA.

Risk factors and prognosis of bone metastases in newly diagnosed gastric cancer.

Aim: To predict the occurrence of bone metastases and prognosis among patients with gastric cancer on a population level. Materials & methods: Data were obtained from the SEER database (2010-2016). Multivariable logistic regression and multivariable Cox regression were used to determine factors that predict the occurrence of bone metastasis and prognosis. Results: Cardia cancer, younger age, white race, poor differentiation grade, higher N stage, diffuse-type were positively associated with the presence of bone metastasis. For gastric cancer patients with bone metastasis, the median survival time was longer (9.0 months) among patients with surgery of primary site compared with those without surgery (3.0 months). Conclusion: According to the results of risk assessment, clinical efforts should be targeted to focus on screening high-risk patients.

Multiwalled carbon nanotubes coated with cobalt(II) sulfide nanoparticles for electrochemical sensing of glucose via direct electron transfer to glucose oxidase.

Multiwalled carbon nanotubes coated with cobalt(II) sulfide nanoparticles were prepared and used for immobilization of glucose oxidase (GOx) to obtain an electrochemical glucose biosensor. The nanocomposite was synthesized through an in-situ hydrothermal method and characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and electrochemical impedance spectroscopy. The results show that the nanocomposite possesses a large specific surface area and apparently enhances the direct electron transfer between GOx and the surface of the electrode, best at a potential near -0.43 V (vs. SCE). The immobilized GOx retains its good bioactivity even at a high surface coverage of 30 pmol cm-2. Under the optimum conditions. The biosensor exhibits a wide linear range (from 8 µM to 1.5 mM), a high sensitivity (15 mA M -1 cm-2), and a 5 µM detection limit (at S/N = 3). The sensor is selective, acceptably repeatable, specific and stable. Graphical abstractMultiwalled carbon nanotubes coated with cobalt(II) sulfide nanoparticles (CoS-MWCNTs) were synthesized through in situ hydrothermal method for the construction of a sensitive electrochemical glucose biosensor.