Pegylated interferon-α-2b combined with tenofovir disoproxil fumarate, granulocyte-macrophage colony-stimulating factor, and hepatitis B vaccine treatment for naïve HBeAg-positive chronic hepatitis B patients: A prospective, multicenter, randomized controlled study.

Hepatitis B surface antigen (HBsAg) loss or seroconversion is an ideal treatment endpoint for patients with chronic hepatitis B but is rarely achievable in  hepatitis B e-antigen (HBeAg)-positive patients using existing treatment strategies. In this study, the effect of pegylated interferon (peg-IFN) alfa-2b plus tenofovir disoproxil fumarate (TDF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and hepatitis B vaccine was evaluated. This randomized controlled trial was conducted at nine liver centers in Chinese university hospitals from May 2018 to July 2020. Patients (n = 303) enrolled were randomly administered peg-IFN-α-2b combined with TDF, GM-CSF, and hepatitis B vaccine (experimental group); peg-IFN-α-2b plus TDF (control group 2); or interferon-α-2b alone (control group 1). The primary efficacy endpoint was HBsAg seroconversion at 48 weeks and the secondary endpoint included safety. No differences in baseline HBsAg levels were observed among the groups. The primary endpoint was achieved in three (3.0%), one (1.03%), and one (1.19%) patient in the experimental group, control group 2, and control group 1, respectively. The incidence of HBsAg seroconversion at week 48 was not significantly different among the three groups (p = 0.629). However, the decrease in serum levels of HBsAg at week 48 was significantly higher in the experimental and control group 2 compared with that in control group 1 (p = 0.008 and 0.006, respectively). No significant difference between the experimental and control group 2 was observed (p = 0.619). Adverse events were not significantly different among the groups except for the lower incidence of neutropenia in the experimental group. Peg-IFN-α-2b combined with TDF, GM-CSF, and hepatitis B vaccine is not superior to peg-IFN-α-2b combined with TDF in HBeAg-positive naïve patients. Clinical Trials Registration: ChiCTR1800016173.

Peroxyacetic Acid Pretreatment: A Potentially Promising Strategy towards Lignocellulose Biorefinery.

The stubborn and complex structure of lignocellulose hinders the valorization of each component of cellulose, hemicellulose, and lignin in the biorefinery industries. Therefore, efficient pretreatment is an essential and prerequisite step for lignocellulose biorefinery. Recently, a considerable number of studies have focused on peroxyacetic acid (PAA) pretreatment in lignocellulose fractionation and some breakthroughs have been achieved in recent decades. In this article, we aim to highlight the challenges of PAA pretreatment and propose a roadmap towards lignocellulose fractionation by PAA for future research. As a novel promising pretreatment method towards lignocellulosic fractionation, PAA is a strong oxidizing agent that can selectively remove lignin and hemicellulose from lignocellulose, retaining intact cellulose for downstream upgrading. PAA in lignocellulose pretreatment can be divided into commercial PAA, chemical activation PAA, and enzymatic in-situ generation of PAA. Each PAA for lignocellulose fractionation shows its own advantages and disadvantages. To meet the theme of green chemistry, enzymatic in-situ generation of PAA has aroused a great deal of enthusiasm in lignocellulose fractionation. Furthermore, mass balance and techno-economic analyses are discussed in order to evaluate the feasibility of PAA pretreatment in lignocellulose fractionation. Ultimately, some perspectives and opportunities are proposed to address the existing limitations in PAA pretreatment towards biomass biorefinery valorization. In summary, from the views of green chemistry, enzymatic in-situ generation of PAA will become a cutting-edge topic research in the lignocellulose fractionation in future.

Facile Construction of i-Motif DNA-Conjugated Gold Nanostars as Near-Infrared and pH Dual-Responsive Targeted Drug Delivery Systems for Combined Cancer Therapy.

Stimuli-responsive DNA-based nanostructures have emerged as promising vehicles for intelligent drug delivery. In this study, i-motif DNA-conjugated gold nanostars (GNSs) were fabricated in a facile manner as stimuli-responsive drug delivery systems (denoted as A-GNS/DNA/DOX) for the treatment of cancer via combined chemo-photothermal therapy. The i-motif DNA is sensitive to the environmental pH and can switch from a single-stranded structure to a C-tetrad (i-motif) structure as the environmental pH decreases from neutral (∼7.4) to acidic (<6.0). The loaded drug can then be released along with the conformational changes. To enhance cellular uptake and improve cancer cell selectivity, the aptamer AS1411, which recognizes nucleolins, was employed as a targeting moiety. The A-GNS/DNA/DOX nanocomposites were found to be highly capable of photothermal conversion and exhibited photostability under near-infrared (NIR) irradiation, and the pH and NIR irradiation effectively triggered the drug-release behaviors. In addition, the A-GNS/DNA/DOX nanocomposites exhibited good biocompatibility. The targeting recognition enabled the A-GNS/DNA/DOX to exhibit higher cellular uptake and therapeutic efficiency than the GNS/DNA/DOX. Notably, under NIR irradiation, a synergistic effect between chemotherapy and photothermal therapy can be achieved with the proposed delivery system, which exhibits much higher therapeutic efficiency both in monolayer cancer cells and tumor spheroids as compared with a single therapeutic method. This study highlights the potential of GNS/DNA nanoassemblies for intelligent anticancer drug delivery and combined cancer therapy.

Multifunctional Fe3O4@Polydopamine@DNA-Fueled Molecular Machine for Magnetically Targeted Intracellular Zn2+ Imaging and Fluorescence/MRI Guided Photodynamic-Photothermal Therapy.

For the precise treatment of tumors, it is necessary to develop a theranostic nanoplatform that has both diagnostic and therapeutic functions. In this article, we designed a new theranostic probe for fluorescence imaging of Zn2+ and fluorescence/MRI guided magnetically targeted photodynamic-photothermal therapy. The fluorescence imaging of Zn2+ was based on an endogenous ATP-driven DNA nanomachine that could perform repetitive stand displacement reaction. It modifies all units on a single PDA/Fe3O4 nanoparticle containing a hairpin-locked initiated strand activated by a target molecule in cells, a two-stranded fuel DNA triggered by ATP, and a two-stranded DNA track responding to an initiated strand and fuel DNA. After entering the cell, the intracellular target Zn2+ initiates the nanomachine via an autocatalytic cleavage reaction, and the machine programmatically and gradually runs on the assembled DNA track via fuel DNA driving and the intramolecular toehold-mediated stand displacement reaction. The Fe3O4 core first exhibits magnetic targeting, increasing the ability of nanoparticles to enter tumor cells at the tumor site. The Fe3O4 could also be employed as a powerful magnetic resonance imaging (MRI) contrast agent and guided therapy. Using 808 nm laser and 635 nm laser irradiation together at the tumor site, the PDA nanoshell produced an excellent photothermal effect and the TMPyP4 molecules entering the cell generated reactive oxygen species, followed by cell damage. A series of reliable experiments suggested that the Fe3O4@PDA@DNA nanoprobe showed superior fluorescence specificity, MRI, a remarkable photothermal/photodynamic therapy effect, and favorable biocompatibility. This theranostic nanoplatform offered a split-new insight into tumor fluorescence and MRI diagnosis as well as effective tumor therapy.

Rattle-Type Gold Nanorods/Porous-SiO2 Nanocomposites as Near-Infrared Light-Activated Drug Delivery Systems for Cancer Combined Chemo-Photothermal Therapy.

Rattle-type nanostructures with movable cores, porous shells, and hollow interiors have become attractive nanoplatforms in the field of nanomedicine, especially for targeted and stimuli-responsive drug delivery. In this work, rattle-type gold nanorods@void@porous-SiO2 (GVPS) nanocomposites were fabricated facilely using the surface-protecting etching method and exhibited high photothermal conversion efficiency. Taking advantage of the porous shell and hollow interior, the nanocomposites have abundant space for drug loading and successfully improved the drug loading capacity up to ∼19.6%. To construct a multifunctional drug delivery system, GVPS was further functionalized with polyethylene glycol (PEG) and cyclic RGD peptides to improve biocompatibility as well as selectivity toward the targeted cancer cells. Besides, to achieve precise regulation and near-infrared laser activation of the drug release, a phase-changing material, 1-tetradecanol (1-TD, Tm: 39 °C), was employed as gatekeepers in this system. After incubation with an αVß3 integrin receptor-overexpressed cell line, the as-prepared GVPSPR-DOX/TD nanocomposites exhibited great performances in combined photothermal therapy and chemotherapy. It is worth noting that the combined therapy showed superior efficiency in cancer cell killing to chemotherapy or photothermal therapy alone.

Design of a Biocompatible and Ratiometric Fluorescent probe for the Capture, Detection, Release, and Reculture of Rare Number CTCs.

Circulating tumor cells (CTCs) served as an important biomarker for tumor recurrence and prediction of prognosis. However, selective capture and quantification of CTCs from whole blood was still full of challenge due to the extremely scare number of CTCs. Moreover, how to keep a high cell viability after capture remained to be solved. Here, we described a ratiometric fluorescent probe for the efficient capture and accurate determination of CTCs by conjugating graphitic carbon nitride quantum dots (g-CNQDs) with gold nanoclusters (AuNCs) and further linking with anti-EpCAM antibody to acquire the CTC-specific immune probe. In this probe, AuNCs protected by albumin V bovine played the role as the fluorophore reference and anti-EpCAM-attached g-CNQDs acted as both the response signal and specific recognition element for sensing CTCs. In the presence of CTCs, the quenched fluorescence of the immune probe at 500 nm was recovered due to the detachment of anti-EpCAM from the probe, whereas the intensity at 650 nm was essentially unchanged. This strategy realized the highly sensitive detection of CTCs in whole blood down to one CTC. Furthermore, it was demonstrated that the designed probe allowed capturing living CTCs with minimal cell damage. The subsequent reculture of captured cells for proliferation revealed that after a 7 day proliferation, almost 28 MCF-7 cells were obtained from one target cell. The immune probe was successfully applied into capture and detection of CTCs from clinical cancer patients. Our data suggested the good potential of fluorescent probe for the clinical diagnosis of cancers.

Effects of Protein Corona on Active and Passive Targeting of Cyclic RGD Peptide-Functionalized PEGylation Nanoparticles.

Protein corona can alter the physiochemical properties of targeting nanoparticles (NPs), as well as their physiological responses and targeting functionality. Herein, we synthesized 20 types of NPs with diverse surface chemistry in order to study the impacts of protein corona on targeting functionality of NPs functionalized with cyclic RGD peptides and their relationships to the polyethylene glycol (PEG) length and grafting density of targeting ligands. After protein adsorption, cyclic RGD on the surface of NP was still able to bind its receptors with increased targeted cellular uptake, even at a relatively low density. However, the cellular uptake was reduced from 26 to 76% when compared with protein nonbound NPs, which was caused by the shielding effect of the outer layer adsorbed proteins. NPs functionalized with short PEG molecules and moderate cyclic RGD density performed a better targeting efficiency. Due to PEG conjugation, the protein corona was demonstrated to be beneficial for passive targeting by decreasing macrophage cellular uptake. These relationships between surface chemistry and targeting functionality will provide guidelines for the design of targeting nanoformulations in nanomedicine.

Baseline quantitative hepatitis B core antibody titre alone strongly predicts HBeAg seroconversion across chronic hepatitis B patients treated with peginterferon or nucleos(t)ide analogues.

OBJECTIVE: The investigation regarding the clinical significance of quantitative hepatitis B core antibody (anti-HBc) during chronic hepatitis B (CHB) treatment is limited. The aim of this study was to determine the performance of anti-HBc as a predictor for hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive CHB patients treated with peginterferon (Peg-IFN) or nucleos(t)ide analogues (NUCs), respectively. DESIGN: This was a retrospective cohort study consisting of 231 and 560 patients enrolled in two phase IV, multicentre, randomised, controlled trials treated with Peg-IFN or NUC-based therapy for up to 2 years, respectively. Quantitative anti-HBc evaluation was conducted for all the available samples in the two trials by using a newly developed double-sandwich anti-HBc immunoassay. RESULTS: At the end of trials, 99 (42.9%) and 137 (24.5%) patients achieved HBeAg seroconversion in the Peg-IFN and NUC cohorts, respectively. We defined 4.4 log10 IU/mL, with a maximum sum of sensitivity and specificity, as the optimal cut-off value of baseline anti-HBc level to predict HBeAg seroconversion for both Peg-IFN and NUC. Patients with baseline anti-HBc ≥4.4 log10 IU/mL and baseline HBV DNA <9 log10 copies/mL had 65.8% (50/76) and 37.1% (52/140) rates of HBeAg seroconversion in the Peg-IFN and NUC cohorts, respectively. In pooled analysis, other than treatment strategy, the baseline anti-HBc level was the best independent predictor for HBeAg seroconversion (OR 2.178; 95% CI 1.577 to 3.009; p<0.001). CONCLUSIONS: Baseline anti-HBc titre is a useful predictor of Peg-IFN and NUC therapy efficacy in HBeAg-positive CHB patients, which could be used for optimising the antiviral therapy of CHB.

Response-guided peginterferon therapy in patients with HBeAg-positive chronic hepatitis B: A randomized controlled study.

BACKGROUND & AIMS: Response-guided therapy has been confirmed to be an effective strategy for the treatment of chronic hepatitis C in the pegylated interferon (PegIFN) era, but no randomized trial utilizing this strategy has been conducted in chronic hepatitis B. METHODS: In this open-label, multicenter, randomized trial, HBeAg positive patients were treated with PegIFN (180µg/week) for 24weeks. Early responders (HBsAg <1500IU/ml and HBV DNA <10(5)copies/ml at week 24) received PegIFN for a further 24weeks (arm A), while non-early responders were randomized to PegIFN for another 24weeks (arm B), another 72weeks (arm C) or PegIFN for another 72weeks plus adefovir for 36weeks (arm D). The primary endpoint was the change of quantitative HBsAg from baseline to the end of follow-up (EOF). RESULTS: For non-early responders, 96-week PegIFN monotherapy did not lead to a greater reduction of HBsAg from baseline to EOF, compared with 48-week PegIFN (-0.71 vs. -0.67log10IU/ml, P=0.407). The rate of HBeAg seroconversion with HBV DNA <2000IU/ml at EOF were similar for arms B, C and D (17.9%, 23.9% and 25.0% respectively). For patients with HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml at week 24, 38.4% and 37.0% achieved HBeAg seroconversion with HBV DNA <2000IU/ml at EOF respectively. CONCLUSIONS: Patients with HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml at week 24 would benefit from continued PegIFN treatment. Extending the duration of PegIFN with or without adding adefovir did not show superiority over 48weeks PegIFN monotherapy. LAY SUMMARY: Extending the duration of pegylated interferon (PegIFN) alfa-2a is not recommended in HBeAg positive patients as treatment extension beyond 48weeks did not show convincing benefit. Patients who achieved HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml after 24-week PegIFNα-2a showed satisfactory outcome after the withdrawal of finite PegIFNα-2a treatment. CLINICAL TRIAL NUMBER: NCT01086085.

Tailorable optical properties of polymer nanodots for triple-mode fluorescence detection of nucleic acids.

We present a triple-mode nanosensor platform for nucleic acid detection utilizing fluorescence anisotropy and Förster resonance energy transfer (FRET) strategies. The self-assembled nanoprobes serve as mass amplifiers, nanoquenchers, or nanodonors, exhibiting high FRET efficiencies (64.4-86.5%) and demonstrating excellent detection capabilities in DNA and microRNA analysis.

Simultaneous determination of monoamines in rat brain with Pt/MWCNTs@Pdop hybrid nanocomposite using capillary electrophoresis--amperometric detection.

In this article, polydopamine (Pdop) functionalized multiwalled carbon nanotubes (MWCNTs@Pdop) were firstly synthesized and employed as the template for the dispersion of Pt nanoparticles to form Pt/MWCNTs@Pdop hybrid nanocomposite. The characterizations of the Pt/MWCNTs@Pdop were investigated by SEM, transmission electron microscopy, x-ray diffraction, and voltammetry. Based upon the Pt/MWCNTs@Pdop nanocomposite, a modified carbon disk electrode was fabricated and successfully applied to the simultaneous detection of four important monoamines, including dopamine, epinephrine, norepinephrine, and serotonin, using capillary electrophoresis--amperometric detection system. Compared with the bare electrode, the four analytes at the Pt/MWCNTs@Pdop electrode exhibited higher sensitivity, broad linear responses from 0.5 to 1.0 × 10(2) nmol/L. The detection limits (S/N = 3) were lower than 9.2 × 10(-10) mol/L. More importantly, the effect of noise exposure on monoamines (MAs) in hippocampus and hypothalamus was investigated for the first time. Compared with the control group, the levels of the MAs all varied to different extents after rats receiving the same noise stimulation. The results showed that the proposed method could be applied to the determination of low levels of MAs in biological samples and screening the target molecules for the diagnosis and treatment of various related diseases.

A liposome-based aptasensor integrated with competitive reaction enabling portable and electrochemical detection of Aß oligomer.

Aggregation of ß-amyloid (Aß) were considered as a typical pathological feature of Alzheimer's disease (AD). Extensive studies have verified that soluble Aß oligomers (AßO) were more toxic to neurons than plaques. Herein, in this work, a glucose entrapped liposome-based portable aptasensor was fabricated for recognizing and interacting with AßO by specific aptamer on liposome (G-Lip-Apt). Then, a single strand DNA, designed to be partially complementary to AßO aptamer, was modified on amino-functionalized Fe3O4@SiO2 to obtain a magnetic nanocomposite (Fe3O4@SiO2/NH2-DNA). In the presence of AßO, the specific recognition between AßO and its aptamer on G-Lip-Apt made AßO bounded with G-Lip-Apt. With subsequent introduction of Fe3O4@SiO2/NH2-DNA, the unreacted G-Lip-Apt was further linked with Fe3O4@SiO2/NH2-DNA by double stranded complementary pairing interaction. Along with the addition of TritonX-100 into the formed G-Lip-Apt/Fe3O4@SiO2/NH2-DNA complex, the encapsulated glucose was released from liposome and then measured by a personal glucose meter (PGM). Good linear correlation was acquired over concentration of 5.0-1000 nM and the limit of detection (LOD) was calculated to be 2.27 nM for AßO. The developed portable electrochemical strategy integrated magnetic separation, competitive reaction and point of care test (POCT) to achieve high sensitivity, selectivity and accuracy, therefore enabled it successfully applied to the analysis of AßO in the hippocampus and cortex of APP/PS1 transgenic AD mice.

A Fast Online Replanning Algorithm Based on Intensity Field Projection for Adaptive Radiotherapy.

Purpose: The purpose of this work was to propose an online replanning algorithm, named intensity field projection (IFP), that directly adjusts intensity distributions for each beam based on the deformation of structures. IFP can be implemented within a reasonably acceptable time frame. Methods and Materials: The online replanning method is based on the gradient-based free form deformation (GFFD) algorithm, which we have previously proposed. The method involves the following steps: The planning computed tomography (CT) and cone-beam CT image are registered to generate a three-dimensional (3-D) deformation field. According to the 3-D deformation field, the registered image and a new delineation are generated. The two-dimensional (2-D) deformation field of ray intensity in each beam direction is determined based on the 3-D deformation field in the region of interest. The 2-D ray intensity distribution in the corresponding beam direction is deformed to generate a new 2-D ray intensity distribution. According to the new 2-D ray intensity distribution, corresponding multi-leaf collimator (MLC), and jaw motion data are generated. The feasibility and advantages of our method have been demonstrated in 20 lung cancer intensity modulated radiation therapy (IMRT) cases. Results: Substantial underdosing in the CTV is seen in the original and the repositioning plans. The average prescription dose coverage (V100%) and D95 for CTV were 100% and 60.3 Gy for the IFP plans compared to 82.6% (P < 0.01) and 44.0 Gy (P < 0.01) for original plans, 86.7% (P < 0.01), and 58.5 Gy (P < 0.01) for repositioning plans. On average, the mean total lung doses were 12.2 Gy for the IFP plan compared to the 12.4 Gy (P < 0.01) and 12.6 Gy (P < 0.01) for the original and the repositioning plans. The entire process of IFP can be completed within 3 min. Conclusions: We proposed an online replanning strategy for automatically correcting interfractional anatomy variations. The preliminary results indicate that the IFP method substantially increased planning speed for online adaptive replanning.

[Preparation and in vitro evaluation of brucine-loaded polylacticacid nanoparticles].

OBJECTIVE: To prepare and evaluate brucine-loaded polylacticacid nanoparticles (Bru-PLA-NPs). METHOD: The Bru-PLA-NPs were prepared by solvent diffusion method. The physical, chemical properties and in vitro release behavior of the prepared Bru-PLA-NPs were evaluated, respectively. RESULT: The mean particle size of the prepared Bru-PLA-NPs was 95 nm with polydispersity index of 0.362. The zeta potential was -15.68 mV. The mean loading and entrapment efficiency of Bru were 7% and 37%, respectively. Compared with Bru solution, an obvious sustained release behavior of Bru from Bru-PLA-NPs was observed in the in vitro release experiment. CONCLUSION: The Bru-PLA-NPs prepared by solvent diffusion method exhibit small particle size, high Bru-loading efficiency, and obvious sustained release in vitro

Nanoformulations of quercetin and cellulose nanofibers as healthcare supplements with sustained antioxidant activity.

Given its health benefits to the human body, quercetin (QT) offers promising applications in the healthcare food and pharmaceutical industries. However, the instability, low water solubility and low bioavailability of QT remain to be solved. In this paper, cellulose nanofiber (CNF) was used as an effective nanoscale carrier to alleviate these problems. By adjusting the solvent composition ratio and processing method, QT was optimally immobilized on CNF surfaces and was eventually encapsulated in the CNF matrices, forming a CNF/QT nanoformulation. A high loading capacity of 78.91% and encapsulation efficiency of 88.77% were achieved simultaneously. The nanoformulation exhibited better dietary performance and antioxidant activity than raw QT. Moreover, sustained release of QT was demonstrated in vitro. These results reveal that CNF is an ideal natural nanoscale dietary carrier and offers high encapsulation efficiency for healthcare supplementation. This work also provides a promising nanoformulation candidate for managing sustained antioxidant requirements.

In vivo monitoring of superoxide anion from Alzheimer's rat brains with functionalized ionic liquid polymer decorated microsensor.

The superoxide anion (O2•-) is an important reactive oxygen species (ROS) in the brain system, which has been associated with the development of many neurological diseases, including Alzheimer's disease (AD). Herein, we introduced a carbon fiber microelectrode (CFME) based in vivo technique for specific and sensitive monitoring of the O2•- radical in the living brains of both normal and AD model rats. Compared with other reported superoxide dismutase (SOD) electrochemical biosensors, the microsensor presented in our work was featured in the coating of a functionalized ionic liquid polymer (PIL) onto PB nanoparticles (PBNPs) and carbon nanotubes (CNT). It was demonstrated that the cationic and carboxyl-rich PILs provided abundant interaction sites with SOD to prevent enzyme leakage from sensor, which was beneficial for the enhancement of sensitivity. Additionally, CCK-8 assay and autoxidation of pyrogallol tests showed that MCF-7 cells maintained a high viability after incubated with PIL and most of the SOD bioactivity was retained in the presence of PIL, which implied the PIL itself possessed an excellent biocompatibility. These properties allow the sensor to track the fluctuation of O2•- levels in vivo between normal and AD rats. This is the first report on application of functionalized PIL to reveal the O2•- related pathological process of AD.

Facile and highly sensitive photoelectrochemical biosensing platform based on hierarchical architectured polydopamine/tungsten oxide nanocomposite film.

The fabrication of photosensitive interface and molecular recognition layer at the biosensing surface are of vital importance in photoelectrochemical (PEC) biosensor construction. Developing facial methods with favorable biomolecule immobilization as well as excellent photoelectric activity still need to be explored. In this work, by integration of the merits of tungsten oxide (WO3) semiconductor nanomaterial and polydopamine (PDA) polymer, a novel biofunctional PDA/WO3 nanocomposites (PDA/WO3 NCs) modified ITO hierarchical architecture was fabricated by simple thermal annealing and self-polymerization methods. The proposed PEC biosensor platform based on PDA/WO3/ITO not only have preponderances in simple preparation, but also possesses excellent PEC activity, high specific surface area and good microenvironment for biomolecule immobilization. Utilizing CYFRA 21-1 as a model target, label-free PEC immunosensor was developed successfully, which exhibited great sensitivity and broad dynamic range with four orders of magnitude (10 pg mL-1 to 100 ng mL-1), and the limit of detection was as low as 2.5 pg mL-1. Moreover, owing to the great sensitivity and selectivity of the proposed platform, this convenient sensor also performed well in real serum sample analysis. It is worth noting that our work not only helps in gaining a better understanding of the applicability of the PEC properties of PDA/WO3 NCs, but also sheds novel light on the design and development of PEC biosensing platform based on PDA/WO3 NCs.

Functional and biocompatible polymeric ionic liquid (PIL) - Decorated immunomagnetic nanospheres for the efficient capture of rare number CTCs.

This work demonstrated an effective strategy for the capture, identification and determination of multiple types of circulating tumor cells (CTCs) on functional and biocompatible immunomagnetic nanosphere interfaces (IMNs). The IMNs were achieved by functionalizing superparamagnetic iron oxide nanospheres (Fe3O4) with polymerized ionic liquid (PIL), and then coating with epithelial-cell-adhesion-molecule antibody (anti-EpCAM). The IMNs exhibited outstanding cell capture efficiency (above 95%) and specificity when employed to separate multiple EpCAM-positive tumor cells, due to the abundant carboxyl groups in the structure of PIL, which enhanced the coupling efficiency of MNs with anti-EpCAM by chemical bonding between carboxyls and amines, thereby enabling more target cells adhered onto IMNs. Under the optimized capture conditions, IMNs were shown an excellent cell capture performance in the range of 5-400 cells/mL in three different cases (e.g., PBS, MCF-7 and THP-1 mixed cell suspension, lysed blood). More significantly, our results indicated that with modification of PIL, in addition to the capture efficiency, the cell viability rate of CTCs was also greatly improved (98%) owing to the nontoxic and biocompatible properties of PIL, which realized the proliferation of the rare number CTCs for further molecular characterization. Finally, the IMNs were successfully applied to the isolation and detection of CTCs in cancer patient peripheral blood samples and as low as one CTC in the whole blood was captured and identified by the ICC method.

Peptide REDV-modified polysaccharide hydrogel with endothelial cell selectivity for the promotion of angiogenesis.

Rapid and controlled vascularization of engineered tissues remains one of the key limitations in thick tissue engineering. Although many studies have focused on improving the rapid vascularization through the immobilization of bioactive molecules, the competition in growth between endothelial cells (ECs) and other cell types is to some extent neglected. In this study, we developed a peptide GREDV-modified scaffold for selective adhesion of human umbilical vein endothelial cells (HUVECs) through the specific recognition of the REDV peptide and integrin α4 ß1 . In vitro studies showed that GREDV-conjugated alginate (ALG-GREDV) improved HUVEC adhesion, migration and proliferation when compared with a non-modified group. Furthermore, ALG-GREDV exhibited a superior capability for promoting the proliferation and selective adhesion of HUVEC over that of other peptide (RGD and YIGSR) modified groups (ALG-Pep). In vivo angiogenic assays demonstrated that the ALG-GREDV scaffold induced an angiogenic potential by stimulating new vessel formation and showed the highest blood vessel density among all samples after 21 days of implanting (83.7 vessels/mm(2) ). More importantly, the blood vessel density in cambium fibrous tissue of ALG-GREDV was about 1.5 times greater than other ALG-Pep groups, indicating facilitation of ALG-GREDV on selective angiogenesis in vivo. These results demonstrated that REDV-conjugated alginate could be a useful scaffold for stimulating and inducing angiogenesis in tissue-engineered applications.

Selective and sensitive determination of uric acid in the presence of ascorbic acid and dopamine by PDDA functionalized graphene/graphite composite electrode.

In this work, a facile electrochemical sensor based on poly(diallyldimethylammonium chloride) (PDDA) functionalized graphene (PDDA-G) and graphite was fabricated. The composite electrode exhibited excellent selectivity and sensitivity towards uric acid (UA), owing to the electrocatalytic effect of graphene nanosheets and the electrostatic attractions between PDDA-G and UA. The anodic peak current of UA obtained by cyclic voltammetry (CV) increased over 10-fold compared with bare carbon paste electrode (CPE). And the reversibility of the oxidation process was improved significantly. Differential pulse voltammetry (DPV) was used to determine UA in the presence of ascorbic acid (AA) and dopamine (DA). It was found that all of oxidation peaks of three species could be well resolved, and the peak current of UA was much stronger than the other two components. More importantly, considerable-amount of AA and DA showed negligible interference to UA assay. The calibration curve for UA ranged from 0.5 to 20 µmol L(-1) with a correlation coefficient of 0.9934. The constructed sensor has been employed to quantitatively determine UA in urine samples.