Wearable Wide-Range Strain Sensors Based on Ionic Liquids and Monitoring of Human Activities.

Wearable sensors for detection of human activities have encouraged the development of highly elastic sensors. In particular, to capture subtle and large-scale body motion, stretchable and wide-range strain sensors are highly desired, but still a challenge. Herein, a highly stretchable and transparent stain sensor based on ionic liquids and elastic polymer has been developed. The as-obtained sensor exhibits impressive stretchability with wide-range strain (from 0.1% to 400%), good bending properties and high sensitivity, whose gauge factor can reach 7.9. Importantly, the sensors show excellent biological compatibility and succeed in monitoring the diverse human activities ranging from the complex large-scale multidimensional motions to subtle signals, including wrist, finger and elbow joint bending, finger touch, breath, speech, swallow behavior and pulse wave.

Adhesive polydopamine-based photothermal hybrid hydrogel for on-demand lidocaine delivery, effective anti-bacteria, and prolonged local long-lasting analgesia.

Considering the astonishing prevalence of localized pain affecting billions of patients worldwide, the development of advanced analgesic formulations or delivery systems to achieve clinical applicability is of great significance. In this study, an integrated PDA-based LiH@PDA@Ag@PAA@Gelatin system was designed for sustained delivery of lidocaine hydrochloride (LiH). By optimizing the preparation process and formulation of the hydrogel, the hydrogel exhibited superior mechanical properties, reversibility, adhesion strength, and self-healing attributes. Moreover, PDA@Ag nanoparticles were evenly dispersed within the hydrogel, and the optimized PDA@Ag@PAA@Gelatin showed a higher photothermal conversion efficiency than that of pure PDA. Importantly, LiH@PDA@Ag@PAA@Gelatin could effectively capture and eradicate bacteria through the synergistic interaction between near-infrared (NIR), PDA, Ag and LiH. In vitro and in vivo tests demonstrated that LiH@PDA@Ag@PAA@Gelatin exhibited higher drug delivery efficiency compared to commercial lidocaine patches. By evaluating the mechanical pain withdrawal threshold of the spared nerve injury (SNI) model in rats, it was proven that LiH@PDA@Ag@PAA@Gelatin enhanced and prolonged the analgesic effect of LiH. Furthermore, LiH@PDA@Ag@PAA@Gelatin induced by NIR possessed excellent on-demand photothermal analgesic ability. Therefore, this study develops a convenient method for preparing localized analgesic hydrogel patches, providing an important step towards advancing PDA-based on-demand pain relief applications.

Identification of fangchinoline as a broad-spectrum enterovirus inhibitor through reporter virus based high-content screening.

Hand, foot, and mouth disease (HFMD) is a common pediatric illness mainly caused by enteroviruses, which are important human pathogens. Currently, there are no available antiviral agents for the therapy of enterovirus infection. In this study, an excellent high-content antiviral screening system utilizing the EV-A71-eGFP reporter virus was developed. Using this screening system, we screened a drug library containing 1042 natural compounds to identify potential EV-A71 inhibitors. Fangchinoline (FAN), a bis-benzylisoquinoline alkaloid, exhibits potential inhibitory effects against various enteroviruses that cause HFMD, such as EV-A71, CV-A10, CV-B3 and CV-A16. Further investigations revealed that FAN targets the early stage of the enterovirus life cycle. Through the selection of FAN-resistant EV-A71 viruses, we demonstrated that the VP1 protein could be a potential target of FAN, as two mutations in VP1 (E145G and V258I) resulted in viral resistance to FAN. Our research suggests that FAN is an efficient inhibitor of EV-A71 and has the potential to be a broad-spectrum antiviral drug against human enteroviruses.

Improved antifouling properties of PVDF membranes modified with oppositely charged copolymer.

Biofouling resulting from the attachment of microorganisms communities to the membrane surface is the major obstacle for the widespread application of membrane technology. This work develops a feasible approach to prepare an anti-biofouling poly(vinylidene fluoride) (PVDF) membrane. A copolymer that possessed oppositely charged groups was first synthesized via radical copolymerization with methyl methacrylate, 2-methacryloxy ethyltrimethyl ammonium chloride and 2-acrylamide-2-methyl propane sulphonic acid as monomers. The copolymer was blended with the PVDF powder to prepare the antifouling membrane via the immersed phase inversion method. The antifouling properties of the modified PVDF membrane were studied by X-ray photoelectron spectroscopy, field emission scanning electron microscopy, water contact angle measurement, zeta-potential measurement, protein adsorption, microbial adhesion and filtration experiments. The modified PVDF membrane showed limited adsorption and adhesion of protein bovine serum albumin and microbes (Escherichia coli and Saccharomyces cerevisiae) with increasing copolymer concentration in the casting solution. The modified PVDF membrane exhibited excellent antibiofouling properties.

A novel micron europium cluster coordination polymer as a strong electrochemiluminescent emitter for accurate and sensitive detection of tetracycline.

In this work, a self-luminescent micron europium cluster coordination polymer (Eu-CCP) cathode electrochemiluminescence (ECL) emitter is first reported. The mass percentage of Eu in Eu-CCP is 50.1%, indicating that Eu-CCP has a high-nucleation luminescence center. In addition, our Eu-CCP possesses a stable and efficient ECL red emission performance, and the intensity is approximately 6.5-fold higher than that of the traditional tris(2,2'-bipyridyl)ruthenium(II) dichloride. The enhancement of Eu-CCP luminescence in our system is due to the following reasons: (1) the mixed ligand and high nuclear europium luminescent center can cooperate to improve the quenching effect induced by water or hydroxyl groups; and (2) external coreaction accelerator and coreactant enhancement. We also investigate the application of Eu-CCP in ECL sensors by sensitive detection of tetracycline (TC). The low detection limit (73.5 fmol·L-1), high selectivity, good stability and satisfactory recoveries indicate that our ECL strategy can be used to detect TC accurately and sensitively.

Laparoscopy-endoscopy Cooperative Surgery for the Treatment of Gastric Gastrointestinal Stromal Tumors.

In view of the shortcomings of endoscopic or laparoscopic surgeries alone in the treatment of gastric gastrointestinal stromal tumors (G-GISTs), this approach makes an innovative improvement in the treatment of G-GISTs that are less than 5 cm in size. Laparoscopy-endoscopy cooperative surgery (LECS) is used to combine endoscopic and laparoscopic surgeries, fully realizing their respective advantages and avoiding their drawbacks. The main steps are as follows. First, gastroscopy and laparoscopy are combined to confirm the location and boundary of the tumor. Tumor resection is carried out laparoscopically, guided by a gastroscope. The specimen is removed orally and the gastric wound closed laparoscopically. Then, gastroscopy and laparoscopy are combined to determine whether there is wound bleeding, if the suture is satisfactory, and if the gastric cavity is deformed. LECS has natural advantages in the treatment of G-GISTs that are less than 5 cm in size. The accurate estimation of tumor location and boundary greatly improves the complete resection rate of tumors. The risk of tumor rupture is substantially reduced, and the long-term prognosis of patients is significantly improved. The process allows for accurate resection of the tumor, maximum preservation of normal gastric tissue and organ function, and avoids postoperative gastric deformation. The patient's postoperative rehabilitation is greatly accelerated, and oral feeding can resume on the day of the operation. The specimen is taken out through the mouth to avoid the need for an extended abdominal incision. This greatly reduces the patient's postoperative pain and scarring. The method greatly shortens the postoperative hospital stay (i.e., discharge is possible on the day after the operation), increasing the turnover of hospital beds.

Resveratrol as a plant type antioxidant modifier for polysulfone membranes to improve hemodialysis-induced oxidative stress.

Resveratrol (RES) is a plant extract with excellent antioxidant, biocompatibility, anti-inflammatory and inhibition of platelet aggregation. RES-modified polysulfone (PSF) hemodialysis membranes have been fabricated using an immersion phase transformation method. The antioxidant properties of the blend membranes were evaluated in terms of their 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS+), reactive oxygen species (ROS) free radicals scavenging, total antioxidant capacity (T-AOC) of serum and lipid peroxidation inhibition. The observed results of decreasing DPPH and ABTS+ levels, scavenging ROS, significant inhibition of lipid peroxidation and improving the T-AOC of serum all contribute to the recovery of oxidative balance and the use of RES as an antioxidant modifier. The antioxidant stability of PSF/RES blend membranes was also studied. Moreover, the results of blood compatibility experiments showed that the addition of RES improved the blood compatibility of PSF membrane, inhibited the adhesion of red blood cells and platelets; inhibited complement activation; and reduced the blood cells deformation rate. The dialysis simulation experiment indicated that PSF/RES membrane (M-3) can clear 90.33% urea, 89.50% creatinine, 74.60% lysozyme and retention 90.47% BSA. All these results showed the new PSF/RES blend membranes have potential to be used in the field of hemodialysis to improve oxidative stress status in patients.

A multifunctional persistent luminescent nanoprobe for imaging guided dual-stimulus responsive and triple-synergistic therapy of drug resistant tumor cells.

We report the design and fabrication of a multifunctional persistent luminescent nanoprobe for imaging guided dual-stimulus responsive and triple-synergistic therapy of drug resistant tumor. The integration of the dual-stimulus of an acidic microenvironment and laser irradiation with the triple-synergistic therapy of doxorubicin, photothermal and siRNA offers excellent therapeutic performance for drug resistant tumor cells with high specificity and little side effects.

Sensitive Deep Ultraviolet Photodetector and Image Sensor Composed of Inorganic Lead-Free Cs3Cu2I5 Perovskite with Wide Bandgap.

In this work, a sensitive deep ultraviolet (DUV) light photodetector based on inorganic and lead-free Cs3Cu2I5 crystalline film derived by a solution method was reported. Optoelectronic characterization revealed that the perovskite device exhibited nearly no sensitivity to visible illumination with wavelength of 405 nm but exhibited pronounced sensitivity to both DUV and UV light illumination with response speeds of 26.2/49.9 ms for rise/fall time. The Ilight/Idark ratio could reach 127. What is more, the responsivity and specific detectivity were calculated to be 64.9 mA W-1 and 6.9 × 1011 Jones, respectively. In addition, the device could keep its photoresponsivity after storage in air environment for a month. It is also found that the capability of Cs3Cu2I5 crystalline film device can readily record still DUV image with acceptable resolution. The above results confirm that the DUV photodetector may hold great potential for future DUV optoelectronic device and systems.

Recognition mechanism of water-compatible molecularly imprinted solid-phase extraction and determination of nine quinolones in urine by high performance liquid chromatography.

Novel water-compatible molecularly imprinted polymers (MIPs) were synthesized in methanol-water systems with ofloxacin as templates and methacryclic acid as functional monomers. The MIPs were used as a special sorbent for the selective solid-phase extraction (SPE) of nine quinolones from urine samples, showing high affinity to the quinolones in aqueous environment. Its molecular recognition mechanisms were investigated by the molecular simulation and the experimental validation with UV and infrared spectrogram as well as (1)H NMR. Binding capability and chromatographic characteristic were also evaluated. By using the water-compatible MIPs as SPE sorbents, the nine quinolones can be selectively extracted and enriched, while all matrices interferences were eliminated simultaneously. Under the optimal conditions of SPE and high performance liquid chromatography (HPLC), the good linearity of the method was obtained in a range of 0.05-30microg/mL with the correlation coefficient of >0.999 and the relative standard division of 2.0-7.4%. The detection limits (s/n=3) were in a range of 0.036-0.10microg/mL. The proposed method was successfully applied for the selective extraction and separation of the studied quinolones in urine samples.

Protective effect of an alpha 7 nicotinic acetylcholine receptor agonist against enterovirus 71 infection in neuronal cells.

Enterovirus 71, as one of the dominant pathogens associated with severe hand, foot, and mouth disease, has been well reported to trigger severe neurological symptoms among young children over the last decade, particularly among children in the Asia-Pacific region. To date, no effective antiviral agent has been developed for the treatment of severe enterovirus 71 infection. PNU-282987, a selective alpha 7 nicotinic acetylcholine receptor (α7nAChR) agonist, has been reported to have a neuroprotective effect by participating in inflammatory regulation in previous studies. Therefore, in the present study, we aimed to assess the cell-protective effect of PNU-282987 against enterovirus 71 infection in neuronal cells, and to discuss potential mechanisms underlying this cell-protective effect in order to elucidate the potential impact of such agonists in the treatment of neurotropic viral infection. We observed that treatment with PNU-282987 improved cell viability and inhibited viral replication in enterovirus 71-infected SH-SY5Y cells. Further investigation revealed that inhibition of enterovirus 71 production by PNU-282987 is likely associated with events of RNA replication, and that increased levels of INF mRNA and its downstream antiviral proteins stimulated by the JAK-STAT2 pathway may contribute to the antiviral effect of PNU-282987. Moreover, our findings suggest that both the antiviral and anti-inflammatory effects of PNU-282987 may contribute to the neural protective effect of the drug in enterovirus 71-infected cells. Taken together, the results suggest that selective α7nAChR agonists may represent viable candidates for future therapeutic treatment of severe enterovirus 71 infection, and for other cases of neurotropic viral infection.

Characteristic of theophylline imprinted monolithic column and its application for determination of xanthine derivatives caffeine and theophylline in green tea.

Theophylline imprinted monolithic columns were designed and prepared for rapid separation of a homologous series of xanthine derivatives, caffeine, and theophylline by an in situ thermal-initiated copolymerization technique. Caffeine and theophylline were fully separated both under isocratic and gradient elutions on this kind of monolithic molecularly imprinted polymers (MIP) column. The broad peak showed in isocratic elution could be improved in gradient elution. Some chromatographic conditions such as mobile phase composition, flow rate, and the temperature on the retention times were investigated. Hydrogen bonding interaction and hydrophobic interaction played an important role in the retention and separation. The binding capacity was evaluated by static adsorption and Scatchard analysis, which showed that the dissociation constant (KD) and the maximum binding capacity (Qmax) were 1.50 mol/L, and 236 micromol/g for high affinity binding site, and 7.97 mol/L and 785 micromol/g for lower affinity binding site, respectively. Thermodynamic data (DeltaDeltaH and DeltaDeltaS) obtained by Van't Hoff plots revealed an enthalpy-controlled separation. The morphological characteristics of monolithic MIP were investigated by scanning electron microscope, which showed that both mesopores and macropores were formed in the monolith. The present monolithic MIP column was successfully applied for the quantitative determination of caffeine and theophylline in different kinds of green tea.

Immunoprotective mechanisms in swine within the "grey zone" in antibody response after immunization with foot-and-mouth disease vaccine.

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals caused by the FMD virus (FMDV). Vaccination represents one approach for limiting the effects of FMD. The level of protection in vaccinated animals after challenge with foot and mouth disease virus (FMDV) is closely related to the antibody titer, which can be classified into three zones: a "white zone", a "grey zone", and a "black zone". The aim of the present study was to clarify the immunoprotective mechanisms operating in the grey zone, in which vaccinated animals have intermediate antibody titers, making it difficult to predict the level of protection. Thirty-three pigs were used to analyze the distribution of lymphocyte subpopulations in whole blood and the expression levels of 40 cytokines before vaccination and challenge. The antibody titer in pigs in the grey zone ranged from 1:6-1:45. Cytotoxic T lymphocyte subpopulations, expression levels of Th1 cytokines such as tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-12, IL-15, IL-18, and monocyte interferon gamma inducing factor (MIG), and of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1α, transforming growth factor-α (TGF-α), and TWEAK R varied between protected and unprotected animals. The results of this study suggest that the cellular immune response is the key factor responsible for immunoprotection in vaccinated animals with antibody titers within the grey zone.

Productive Entry of Foot-and-Mouth Disease Virus via Macropinocytosis Independent of Phosphatidylinositol 3-Kinase.

Virus entry is an attractive target for therapeutic intervention. Here, using a combination of electron microscopy, immunofluorescence assay, siRNA interference, specific pharmacological inhibitors, and dominant negative mutation, we demonstrated that the entry of foot-and-mouth disease virus (FMDV) triggered a substantial amount of plasma membrane ruffling. We also found that the internalization of FMDV induced a robust increase in fluid-phase uptake, and virions internalized within macropinosomes colocalized with phase uptake marker dextran. During this stage, the Rac1-Pak1 signaling pathway was activated. After specific inhibition on actin, Na(+)/H(+) exchanger, receptor tyrosine kinase, Rac1, Pak1, myosin II, and protein kinase C, the entry and infection of FMDV significantly decreased. However, inhibition of phosphatidylinositol 3-kinase (PI3K) did not reduce FMDV internalization but increased the viral entry and infection to a certain extent, implying that FMDV entry did not require PI3K activity. Results showed that internalization of FMDV exhibited the main hallmarks of macropinocytosis. Moreover, intracellular trafficking of FMDV involves EEA1/Rab5-positive vesicles. The present study demonstrated macropinocytosis as another endocytic pathway apart from the clathrin-mediated pathway. The findings greatly expand our understanding of the molecular mechanisms of FMDV entry into cells, as well as provide potential insights into the entry mechanisms of other picornaviruses.

Quantitative Detection of the Foot-And-Mouth Disease Virus Serotype O 146S Antigen for Vaccine Production Using a Double-Antibody Sandwich ELISA and Nonlinear Standard Curves.

The efficacy of an inactivated foot-and-mouth disease (FMD) vaccine is mainly dependent on the integrity of the foot-and-mouth disease virus (FMDV) particles. At present, the standard method to quantify the active component, the 146S antigen, of FMD vaccines is sucrose density gradient (SDG) analysis. However, this method is highly operator dependent and difficult to automate. In contrast, the enzyme-linked immunosorbent assay (ELISA) is a time-saving technique that provides greater simplicity and sensitivity. To establish a valid method to detect and quantify the 146S antigen of a serotype O FMD vaccine, a double-antibody sandwich (DAS) ELISA was compared with an SDG analysis. The DAS ELISA was highly correlated with the SDG method (R2 = 0.9215, P<0.01). In contrast to the SDG method, the DAS ELISA was rapid, robust, repeatable and highly sensitive, with a minimum quantification limit of 0.06 µg/mL. This method can be used to determine the effective antigen yields in inactivated vaccines and thus represents an alternative for assessing the potency of FMD vaccines in vitro. But it still needs to be prospectively validated by analyzing a new vaccine preparation and determining the proper protective dose followed by an in vivo vaccination-challenge study to confirm the ELISA findings.

Preliminary investigation on hemocompatibility of poly(vinylidene fluoride) membrane grafted with acryloylmorpholine via ATRP.

This work provides a promising way to improve the hemocompatibility of PVDF membrane. An amphiphilic copolymer (PVDF-g-PACMO) having PVDF backbones and poly(N-acryloylmorpholine) (PACMO) side chains was synthesized via atom transfer radical polymerization (ATRP). It is found that the grafting degree of the PACMO increases linearly with the increase of ACMO concentration in the reaction solution. The PVDF-g-PACMO membrane was prepared via immersed phase inversion method. The structure and performances were evaluated by X-ray photoelectron spectroscopy, field emission scanning electron microscopy, water contact angle, and filtration experiment. The hemocompatibility of the membranes were preliminarily investigated by protein adsorption, platelet adhesion, anticoagulant evaluation and hemolysis test. The results indicate that the PVDF membrane functionalized by PACMO can suppress the protein adsorption and platelet adhesion, and shows an improved hemocompatibility.

Biocompatible chiral monolithic stationary phase synthesized via atom transfer radical polymerization for high performance liquid chromatographic analysis.

Novel biocompatible chiral monolithic stationary phase was prepared by reverse and direct atom transfer radical polymerization (ATRP) methods. By taking advantages of the controlled/living property of ATRP method, the chiral monolith was prepared by reverse ATRP (RATRP) firstly. An attractive feature of RATRP is the prepared polymer containing a terminal radically transferable atom that can initiate another post-polymerization reaction by direct ATRP. Then, the biocompatible poly(hydroxyethyl methacrylate) (PHEMA) was grafted on the surface of the chiral monolith by direct ATRP as a diffusion barrier for proteins. This biocompatible chiral monolith was successfully used as restricted access stationary phase for determination of enantiomers in biological samples with direct injection by high-performance liquid chromatography (HPLC).

Quantitative Proteomic Analysis of BHK-21 Cells Infected with Foot-and-Mouth Disease Virus Serotype Asia 1.

Stable isotope labeling with amino acids in cell culture (SILAC) was used to quantitatively study the host cell gene expression profile, in order to achieve an unbiased overview of the protein expression changes in BHK-21 cells infected with FMDV serotype Asia 1. The SILAC-based approach identified overall 2,141 proteins, 153 of which showed significant alteration in the expression level 6 h post FMDV infection (57 up-regulated and 96 down-regulated). Among these proteins, six cellular proteins, including three down-regulated (VPS28, PKR, EVI5) and three up-regulated (LYPLA1, SEC62 and DARs), were selected according to the significance of the changes and/or the relationship with PKR. The expression level and pattern of the selected proteins were validated by immunoblotting and confocal microscopy. Furthermore, the functions of these cellular proteins were assessed by small interfering RNA-mediated depletion, and their functional importance in the replication of FMDV was demonstrated by western blot, reverse transcript PCR (RT-PCR) and 50% Tissue Culture Infective Dose (TCID50). The results suggest that FMDV infection may have effects on the expression of specific cellular proteins to create more favorable conditions for FMDV infection. This study provides novel data that can be utilized to understand the interactions between FMDV and the host cell.

Homogeneous modification of cellulose in ionic liquid with succinic anhydride using N-bromosuccinimide as a catalyst.

The homogeneous chemical modification of cellulose with succinic anhydride was investigated in a solvent system containing 1-butyl-3-methylimidazolium chloride ionic liquid and dimethylsulfoxide using N-bromosuccinimide (NBS) as a catalyst. The results showed that the degree of substitution of the succinylated cellulosic samples, in the range of 0.24-2.31, noticeably increased as compared with the products without any catalysts, indicating that NBS was a novel efficient catalyst for cellulose succinoylation in ionic liquids. Fourier transform infrared and solid-state cross-polarization/magic angle spinning (13)C NMR spectroscopies also provided evidence of succinoylation reaction. The results indicated that the reaction of hydroxyl groups at C-6, C-2, and C-3 positions in cellulose occurred. The thermal stability of the succinylated cellulose was found to decrease upon chemical modification.

[Synthesis and screening of polyethylenimine as a carrier for gene transfer into cultured human tumor cells].

BACKGROUND & OBJECTIVE: Choosing suitable gene carrier is very important in gene therapy. Recently, polyethylenimine (PEI), a new polycation compound, is particularly attractive due to its high transduction efficiency and low toxicity. This study was to synthesize a series of PEI nanogels of different particle diameters by photochemistry, investigate the relation between the transfection efficiency and particle diameter, and screen ideal gene carrier. METHODS: PEI nanogels were synthesized by photochemistry. The particle diameter was detected by photo correlation spectroscopy (PCS). The spherical morphology of the nanogels was characterized by scanning electron microscopy (SEM), and confirmed by atomic force microscopy (AFM). Using PEI/DNA complex as a plasmid vector, the enhanced green fluorescence protein (EGFP) gene was transferred into Bel7402 and A549 cells. Gene expression was quantitatively evaluated by fluorescent microscopy and flow cytometry (FCM). RESULTS: The diameter of synthesized PEI nanogels was in the range of 80-200 nm, and most of them were globular. The delivery rate reached the maximum when using 4 microg PEI (86.9 nm) to transfer 2 microg EGFP: the delivery rates were (32.75+/-1.01)% for Bel7402 cells and (29.81+/-1.84)% for A549 cells when detected by fluorescent microscopy, and were (32.40+/-1.41)% for Bel7402 cells and (30.00+/-1.86)% for A549 cell when detected by FCM. There was no significant difference between PEI and LipofectamineTM 2000 in the transfection efficiency (P > 0.05). CONCLUSIONS: PEI nanogels synthesized by photochemistry are effective nonviral vectors for gene delivery into human tumor cells in vitro. The transfection efficiency of 86.9 nm PEI is the highest.