Dummy-surface molecularly imprinted polymers as a sorbent of micro-solid-phase extraction combined with dispersive liquid-liquid microextraction for determination of five 2-phenylpropionic acid NSAIDs in aquatic environmental samples.

A highly binding dummy template surface of molecularly imprinted polymers (MWNTs-MIPs) was synthesized on multi-walled carbon nanotubes surface using 2-phenylpropionic acid as dummy template, 4-vinylpyridine as the functional monomer, ethylene glycol dimethacrylate as the cross-linker, and DMF as porogen by precipitation polymerization method. MIPs were characterized by FT-IR spectroscopy, scanning electron microscope, thermo-gravimetric analysis, and nitrogen adsorption-desorption experiment. Adsorption and selectivity experiments of MIPs and non-imprinted polymers (NIPs) verified that the MIPs had a good selectivity and adsorption properties for five 2-phenylpropionic acid nonsteroidal anti-inflammatory drugs (NSAIDs). Imprinted polymer was used as a sorbent material for µSPE in current work and µSPE-DLLME method was selected for pretreatment of water samples. The µSPE-DLLME method was successfully used for the pre-concentration of five non-steroidal anti-inflammatory drugs in different environmental water samples prior to ultra-high performance liquid chromatography-tandem mass spectrometry. Efficiencies of µSPE and DLLME were thoroughly investigated and optimized in this study. The optimal results were obtained by using 3 mL of 1% formic acid-acetonitrile as elution solvent and dichloroethane and acetonitrile as extractant and disperser solvent, respectively. Limits of detection and quantification of five NSAIDs for different water matrices varied from 0.50 to 1.10 ng L-1 and 0.93 to 2.20 ng L-1, respectively. Each target analyte had a good linearity in its corresponding concentration range. Enrichment factors of target analytes ranged from 91 to 215. Recoveries of the target analytes were between 72.43 and 113.99% at the concentration levels of 0.02, 0.1, and 0.5 µg L-1. The developed method was successfully applied to extraction and analysis of NSAIDs in different water samples with satisfactory results which could help us better understand their environmental fate and risk to ecological health. Graphical abstract Dummy-surface molecularly imprinted polymers as a sorbent of micro-solid-phase extraction combined with dispersive liquid-liquid microextraction for determination of five 2-phenylpropionic acid NSAIDs in aquatic environmental samples.

Loss of lysyl oxidase-like 3 causes cleft palate and spinal deformity in mice.

In mammals, embryonic development are highly regulated morphogenetic processes that are tightly controlled by genetic elements. Failure of any one of these processes can result in embryonic malformation. The lysyl oxidase (LOX) family genes are closely related to human diseases. In this study, we investigated the essential role of lysyl oxidase-like 3 (LOXL3), a member of the LOX family, in embryonic development. Mice lacking LOXL3 exhibited perinatal lethality, and the deletion of the Loxl3 gene led to impaired development of the palate shelves, abnormalities in the cartilage primordia of the thoracic vertebrae and mild alveolar shrinkage. We found that the obvious decrease of collagen cross-links in palate and spine that was induced by the lack of LOXL3 resulted in cleft palate and spinal deformity. Thus, we provide critical in vivo evidence that LOXL3 is indispensable for mouse palatogenesis and vertebral column development. The Loxl3 gene may be a candidate disease gene resulting in cleft palate and spinal deformity.

Chitosan quaternary ammonium salt/gelatin-based biopolymer film with multifunctional preservation for perishable products.

The postharvest physiological and metabolic activities caused fruits and vegetables (F&V) quality deterioration. Therefore, developing an efficient preservation strategy is a promising approach to relieve this issue. In this study, a modified metal-organic framework (MOF; i.e., Cer@MHKUST-1) was encapsulated into a blended matrix of chitosan quaternary ammonium salt (CQAS)/gelatin to fabricate a multifunctional (water-locking, ethylene-removing, and antibacterial) packaging biopolymer-based film (i.e., CMCGF), the characteristics and preservative effects of the packaging were investigated. Results indicated that the physicochemical (e.g., mechanical, gas/light barrier, wettability) properties of CMCGF were improved compared with the control film (i.e., CGF). CMCGF have a higher ethylene adsorption performance of 65-69 cm3/g STP compared with CGF (7.8 cm3/g STP). Cu ions released from CMCGF destroyed the cell wall and membrane, resulting in the death of bacteria, and the antibacterial efficiency of CMCGF against E. coli and S. aureus was 97-100 % and 98-100 %, respectively. Postharvest storage experiments on tomato and winter jujube confirmed the high-efficiency preservation effect of CMCGF packaging. Therefore, CMCGF provides a multifunctional approach to extending the shelf-life of perishable products to decrease food wastage.

Interaction mechanisms of peanut protein isolate and high methoxyl pectin with ultrasound treatment: The effect of ultrasound parameters, biopolymer ratio, and pH.

Ultrasound could effectively change molecular structure of proteins, polysaccharides, and their interactions, and was used to treat the peanut protein isolate-high methoxy pectin (PPI-HMP) complexes in this study. Effects of different ultrasound parameters, PPI-HMP mixing ratio (40:1-5:2), and pH (2.0-8.0) on the PPI-HMP interactions were investigated. Turbidity, solution appearance, and Zeta-potential analysis revealed an electrostatic interaction between PPI and HMP from pH 2.0 to pH 6.0. Ultrasound changed the tertiary structure conformation of PPI according to the surface hydrophobicity analysis. Increased ultrasound power density and pH broke the hydrogen bonds between the complexes according to Fourier transform infrared spectroscopy analysis. Apparent viscosity and confocal laser scanning microscopy analysis showed that appropriate ultrasound treatment (5.43 W/cm3, 25 min, 25 °C) reduced the viscosity of the complexes, and enhanced the electrostatic and hydrophobic interactions between PPI and HMP. These findings will contribute to the application of PPI-HMP complexes in the food industry.

Immobilization of α-galactosidase in polyvinyl alcohol-chitosan-glycidyl methacrylate hydrogels based on directional freezing-assisted salting-out strategy for hydrolysis of RFOs.

Raffinose family oligosaccharides (RFOs) in food are the main factors causing flatulence in Irritable Bowel Syndrome (IBS) patients and the development of effective approaches for reducing food-derived RFOs is of paramount importance. In this study, polyvinyl alcohol (PVA)-chitosan (CS)-glycidyl methacrylate (GMA) immobilized α-galactosidase was prepared by the directional freezing-assisted salting-out technique, aimed to hydrolyze RFOs. SEM, FTIR, XPS, fluorescence and UV characterization results demonstrated that α-galactosidase was successfully cross-linked in the PVA-CS-GMA hydrogels, forming a distinct porous stable network through the covalent bond between the enzyme and the carrier. Mechanical performance and swelling capacity analysis illustrated that α-gal @ PVA-CS-GMA not only had suitable strength and toughness for longer durability, but also exhibited high water content and swelling capacity for better retention of catalytic activity. The enzymatic properties of α-gal @ PVA-CS-GMA showed an improved Km value, pH and temperature tolerance range, anti-enzymatic inhibitor (melibiose) activity compared to the free α-galactosidase and its reusability was at least 12 times with prolonged storage stability. Finally, it was successfully applied in the hydrolysis of RFOs in soybeans. These findings provide a new strategy for the development of α-galactosidase immobilization system to biological transform the RFOs components in the food for diet intervention of IBS.

Carboxymethyl chitosan-decorated proliposomes as carriers for improved stability and sustained release of flaxseed oil.

A flaxseed oil carboxymethyl chitosan-decorated proliposome system was fabricated in this research. The physicochemical characteristics, stability, and in vitro release behaviors of flaxseed oil were studied and compared with that of flaxseed oil-loaded liposomes. The results of dynamic light scattering, transmission electron microscopy, and oxidation stability indicated that the storage stability of proliposomes was better. After 28 days of storage, the peroxide value of flaxseed oil-loaded liposomes (20.1 meq/kg) was significantly (P < 0.05) higher than that of flaxseed oil-loaded proliposomes (9.0 meq/kg); the thiobarbituric acid reactive substances in the former (0.53 mmol/kg) was also higher than that in the latter (0.27 mmol/kg). The in vitro release behavior of flaxseed oil indicated the proliposomes were more stable in the simulated gastrointestinal fluids. Therefore, the flaxseed oil-loaded proliposome system could be a promising vehicle for delivery flaxseed oil in food industry. PRACTICAL APPLICATION: A flaxseed oil-loaded proliposome delivery system was fabricated in this research. Their physical and oxidation stability of flaxseed oil were improved, and the in vitro cumulative release of flaxseed oil was delayed compared with flaxseed oil liposomes. This system may provide an effective strategy for the flaxseed oil encapsulation in the food industry.

Treatment outcomes after reduction of the target volume of intensity-modulated radiotherapy following induction chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: A prospective, multi-center, randomized clinical trial.

PURPOSE: To investigate whether reducing the target volume of intensity-modulated radiotherapy (IMRT) after induction chemotherapy (IC) improves the quality of life (QOL) in locoregionally advanced nasopharyngeal carcinoma (NPC) without decreasing the local control and survival rate. PATIENTS AND METHODS: A total number of 212 NPC patients staged as III-IVb were randomly assigned to group A (n=97) or group B (n=115) in this prospective clinical trial. All patients received IC followed by cisplatin concurrent with IMRT. IMRT was planned using the images of pre-IC in group A and post-IC in group B. RESULTS: The dose received by normal tissues in group B was lower than that of group A (P<0.05). The recovery of the dry mouth symptoms in group B was significantly improved than group B. The quality of life (QOL) scores in group B were higher than group A. With a median follow-up of 35months, the 1-year estimated overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS) in group A versus group B were 97.9% vs 97.3%, 90.7% vs 92,2%, 99.0% vs 98.2%, 91.8% vs 94.8%. The 2-year OS, PFS, LRFFS, DMFS in group A versus group B were 93.7% vs 92.9%, 83.4% vs 84.3%, 96.8% vs 95.5%, 86.5% vs 89.5%. The 3-year OS, PFS, LRFFS, DMFS in group A versus group B were 82.3% vs 87%, 74.7% vs 83.4%, 91.8 vs 93.9%, 81.3% vs 88.6%, respectively. CONCLUSION: Reducing the IMRT target volume after IC did not reduce the local control and survival rate in locoregionally advanced NPC but the doses received by normal tissues were decreased, and the QOL scores were improved.

Novel composite drug delivery system as a novel radio sensitizer for the local treatment of cervical carcinoma.

In this study, we investigated in vivo radiosensitizing effects of a gel-based dual drug delivery system (DDS) (PECE/DDP + mPEG-PCL/PTX, or PDMP) in a cervical cancer model, and determined its possible mechanisms of action. A xenograft cervical cancer model was used to investigate the radio sensitization effect of PDMP. Mice underwent paclitaxel (PTX) + cisplatin (DDP), PECE, or PDMP treatment followed by single radiation doses ranging from 0 Gy to 20 Gy. Radio sensitization was analyzed by tumor regrowth delay (TGD). The sensitization enhancement ratio (SER) was calculated by the doses needed to yield TGD when using radiation treatment alone and when using radiation plus drug treatment. The impact of irradiation and drugs on TGD was determined, and an optimum radiation dose was chosen for further evaluation of radio sensitizing effects. The data showed that PDMP yielded the highest radio sensitization (SER was 1.3) and a radiation dose of 12 Gy was chosen for further investigation. PDMP + radiotherapy treatment was most effective in inhibiting tumor growth, prolonging survival time, decreasing expression of CD31, CD133, and aldehyde dehydrogenase 1 (ALDH1), inducing G2/M phase arrest, apoptosis, and expression of Ataxia telangiectasia mutated (ATM) and histone H2AX phosphorylation (γ-H2AX). Thus, our data indicated that PDMP is a promising anti-tumor and radio sensitization reagent for the treatment of cervical carcinoma.

In vivo synergistic anti-tumor effect of paclitaxel nanoparticles combined with radiotherapy on human cervical carcinoma.

In this study, our purpose was to explore the synergistic anti-tumor effect and mechanism of paclitaxel nanoparticles (PTX-NPs) combined with radiotherapy (RT) on human cervical carcinoma (HeLa). PTX-NPs were prepared by a solid dispersion method using methoxy poly(ethylene glycol)-poly(ɛ-caprolactone) (MPEG-PCL), which combined with RT exerted a potent and high efficient effect against cervical cancer. In vivo antitumor activity of PTX-NPs combined with RT, was estimated using nude mice carrying Hela cell xenograft tumor. The results were evaluated using microfluorine-18-deoxyglucose PET/computed tomography (18F-FDG PET/CT) and immunohistochemistry. The results showed that PTX-NPs possessed a more efficient effect than PTX when combined with RT (p < 0.05). PTX-NPs in combination with RT might inhibit cell proliferation through its action on Ki-67, and decreased micro-vessel density (MVD) associated with CD31 and vascular endothelial growth factor (VEGF). These results suggested that PTX-NPs possessed a synergistic anti-tumor effect against cervical cancer when combined with RT.

Construction of Finite Element Model for an Artificial Atlanto-Odontoid Joint Replacement and Analysis of Its Biomechanical Properties.

AIM: To investigate the stress distribution on artificial atlantoaxial-odontoid joint (AAOJ) components during flexion, extension, lateral bending and rotation of AAOJ model constructed with the finite element (FE) method. MATERIAL AND METHODS: Human cadaver specimens of normal AAOJ were CT scanned with 1 mm -thickness and transferred into Mimics software to reconstruct the three-dimensional models of AAOJ. These data were imported into Freeform software to place a AAOJ into a atlantoaxial model. With Ansys software, a geometric model of AAOJ was built. Perpendicular downward pressure of 40 N was applied to simulate gravity of a skull, then 1.53 N• m torque was exerted separately to simulate the range of motion of the model. RESULTS: An FE model of atlantoaxial joint after AAOJ replacement was constructed with a total of 103 053 units and 26 324 nodes. In flexion, extension, right lateral bending and right rotation, the AAOJ displacement was 1.109 mm, 3.31 mm, 0.528 mm, and 9.678 mm, respectively, and the range of motion was 1.6°, 5.1°, 4.6° and 22°. CONCLUSION: During all ROM, stress distribution of atlas-axis changed after AAOJ replacement indicating that AAOJ can offload stress. The stress distribution in the AAOJ can be successfully analyzed with the FE method.

A study of the synergistic effect of folate-decorated polymeric micelles incorporating Hydroxycamptothecin with radiotherapy on xenografted human cervical carcinoma.

In this study, Hydroxycamptothecin (HCPT)-loaded micelles were formed in water by the self-assembly of folate (FA)-decorated amphiphilic block copolymer, methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL), and achieved a hydrodynamic diameter about of 132 nm. HCPT release from the micelles exhibited no initial burst but showed a sustained release profile. The cytotoxicity and targeting ability of FA conjugated polymeric micelles was investigated by using methylthiazoletetrazolium (MTT) and fluorescence microscopy. We found that FA-conjugated micelles had superior cytotoxicity against HeLa cells compared to non-conjugated micelles, and that they exerted this effect by folate receptor (FR)-mediated endocytosis. In addition, HeLa cells were xenografted into nude mice and subjected to radiotherapy (RT) and/or HCPT-loaded micelle treatment. The antitumor efficacy was detected by analysis of tumor growth delay (TGD) and median survival time. Micro fluorine-18-deoxyglucose PET/computed tomography ((18)F-FDG PET/CT) was performed to assess early tumor response to HCPT-loaded micelles in combination with RT. Analysis of cell cycle redistribution, apoptosis and expression of histone H2AX phosphorylation (λ-H2AX) was used to evaluate the mechanism by which HCPT loaded micelles led to radiosensitization. Taken together, the results showed that HCPT-loaded FA decorated micelles efficiently sensitized xenografts in mice to RT, and induced G2/M phase arrest, apoptosis and expression of λ-H2AX.

A Novel Anterior Odontoid Screw Plate for C1-C3 Internal Fixation: An In Vitro Biomechanical Study.

STUDY DESIGN: A biomechanical in vitro study was performed using a standardized experimental protocol in a biomechanical spine testing apparatus. OBJECTIVE: The aims of this study were to evaluate the biomechanical stability afforded by 4 cervical fixation techniques: anterior cervical plate+odontoid screw+cage (ACP+OS+cage), anterior odontoid screw plate+bone graft (AOSP+bone graft), posterior C2-3 fixation+odontoid screw (C2PS+C3LMS+OS), and posterior C1-3 fixation (C1PS+C2PS+C3LMS). SUMMARY OF BACKGROUND DATA: Unstable axis injuries with multiple fracture lines are uncommon injuries, and their management is still challenging for surgeons who aim to achieve primary stability, early mobilization, preserved cervical range of motion (ROM), and favorable outcome. We designed a novel AOSP to assist in this challenging clinical scenario. METHODS: Eight fresh-frozen cadaveric spine specimens (C1-C3) were subjected to stepwise destabilization of the C1-3 complex, with serial replication of a type II Hangman fracture, a type II odontoid fracture, and a C2 to C3 disc injury. Intact specimens, destabilized specimens, and destabilized specimens with various stabilization techniques including anterior and posterior techniques, some using our AOSP, were each tested for stability. Each spine was subjected to flexion, and extension testing, left and right lateral bending, and left and right rotation. RESULTS: After AOSP+bone graft fixation, the ROMC2-C3 during all loading modes were reduced to values that were significantly less than normal. During all loading modes, AOSP+bone graft fixation significantly outperformed the ACP+OS+cage fixation in limiting ROMC2-C3. During flexion and extension, AOSP+bone graft fixation significantly outperformed the C1PS+C2PS+C3LMS fixation and C2PS+C3LMS+OS fixation in limiting ROMC2-C3. CONCLUSION: The AOSP has excellent biomechanical performance when dealing with type I Hangman fractures, type II odontoid fractures, and C2-3 disc injuries. The AOSP+one graft fixation can preserve the function of atlanto-axial joint, which may be a valuable stabilization strategy for these unique injuries.