Aptamer-based biosensing through the mapping of encoding upconversion nanoparticles for sensitive CEA detection.

A sensitive detection system based on aptamer-based biosensors for the detection of carcinoembryonic antigen (CEA) by mapping encoding upconversion nanoparticles (UCNPs) was constructed. In this sensor, oligonucleotides with CEA aptamer fragments immobilized on magnetic beads (MBs) were hybridized to complementary DNA modified on UCNPs (cDNA-UCNPs); thus, sandwich-structured probes were formed. In the presence of CEA, due to the stronger interaction between the aptamer and CEA than that of the aptamer and complementary DNA on UCNPs, the cDNA-UCNPs were isolated from the MBs, and the number of isolated UCNPs was directly related to the concentration of CEA. Using an inverted fluorescence microscope, the number of target-dependent UCNPs on a glass slide was counted, enabling the accurate determination of CEA in the solution. The dynamic range for CEA detection in PBS buffer was 0.02-6.0 ng mL-1 (0.1-30 pM) and a limit of detection (LOD) of 65 fM was achieved. We envisage that the system we developed can also have many promising applications in the sensitive detection of other biomarkers for early cancer diagnosis.

Optical weak measurement for the precise thickness determination of an ultra-thin film.

A total internal reflection system based on the weak value amplification principle is set up for the precise measurement of the thickness of an ultra-thin film. In this system, the film thickness is derived from the change of the double-peak pointer caused by the effective refractive index of the film, which is correlated to its thickness. The sensitivity and resolution of this system reached 2727.21 nm/RIU and 7.2×10-6 R I U, respectively, determined by using a sodium chloride solution with a refractive index of 1.331911. The growth process of TA/Fe(III) assembled films with thicknesses in the few nanometers range is monitored using the as-set-up system, and the experimental results are consistent with a theoretical calculation based on the Maxwell Garnett effective medium. Additionally, we theoretically calculated the detection limit for the thickness measurement of the film as 22 pm. We clearly provide a potential method for the precise measurement of the thickness of an ultra-thin film.

Microfluidic synthesis of Janus-structured QD-encoded magnetic microbeads for multiplex immunoassay.

Uniform and monodisperse quantum dot (QD)-encoded magnetic microbeads with Janus structure were produced in a microfluidic device via photopolymerization. UV light through a microscope objective was used to solidify the microbeads which showed sharp interfaces and excellent magnetic responses. QDs with different emission peaks (450 nm for blue and 640 nm for red) were mixed at different ratios to provide three spectral codes. The QD-encoded microbeads can be distinguished by analyzing their fluorescent images in HSV color space. After hydrolysis of the anhydride group in alkaline solution, protein was immobilized on microbeads via activation of carboxyl groups using (1-ethyl-3(3-dimethylaminoprophyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS). A microhole array in polydimethylsiloxane (PDMS) substrates with a specific size was fabricated to trap individual microbeads in a single microhole. The combination of Janus-structured QD-encoded magnetic microbeads and microhole arrays facilitates both flexibility, binding kinetics, sensitivity for suspension assay, and fluorescence mapping analysis for conventional biochips, thus providing a novel platform for multiplex bioanalysis. The capability of this integration for multiplex immunoassays was verified using three kinds of IgG and their corresponding anti-IgG. A detection limit of 0.07 ng/mL was achieved for human IgG, indicating practical applications in various fields.

Determination of 11 minerals in children using inductively coupled plasma mass spectrometry.

BACKGROUND: Minerals play an important role in children's growth and cognition. In this study, our aim was to establish reference intervals of mineral level in Children of Liaoning province (China) and provide a reliable basis for future preventive healthcare guidelines. METHODS: Random samples of 2217 healthy children aged 0-15 years who were referred for routine hospital laboratory examinations in the cities of Shenyang, Fushun, Fuxin, Benxi, Chaoyang and Lingyuan were invited to participate in the study. Serum levels of Calcium (Ca), Iron (Fe), Zinc (Zn), Magnesium (Mg), Copper (Cu), Manganese (Mn), Selenium (Se), Mercury (Hg), Nickel (Ni), Cobalt (Co), and Lithium (Li) were determined by inductively coupled plasma mass spectrometer(ICP-MS). RESULTS: Sex-related significant differences in the serum concentrations of the Mg and Cu (P < 0.05). Age-related significant differences were found in serum levels of Ca, Fe, Zn, Mg, Cu and Mn (P < 0.05) and the concentrations of 9 minerals (Ca, Mg, Cu, Mn,Se,Hg,Ni,Co and Li in serum varied from season to season (P < 0.05). The Spearman correlation matrix of 11 minerals was shown as a heat map, the correlations between Ca-Zn, Ca-Mg, Fe-Zn, Fe-Se, Mn-Ni, Se-Hg, Se-Ni, Hg-Ni, and Ni-Co, Ni-Li were the strongest compared with others. CONCLUSIONS: The reference intervals of serum 11 minerals for children should considering the sex, age and season, which may be useful for decisive diagnoses of abnormality of the 11minerals and the related diseases.

A Sensitive and Stable Surface Plasmon Resonance Sensor Based on Monolayer Protected Silver Film.

In this paper, we present a stable silver-based surface plasmon resonance (SPR) sensor using a self-assembled monolayer (SAM) as a protection layer and investigated its efficiency in water and 0.01 M phosphate buffered saline (PBS). By simulation, silver-based SPR sensor has a better performance in field enhancement and penetration depth than that of a gold-based SPR sensor, which are 5 and 1.4 times, respectively. To overcome the instability of the bare silver film and investigate the efficiency of the protected layer, the SAM of 11-mercapto-1-undecanol (MUD) was used as a protection layer. Stability experiment results show that the protected silver film exhibited excellent stability either in pure water or 0.01 M PBS buffer. The sensitivity of the silver-based SPR sensor was calculated to be 127.26 deg/RIU (refractive index unit), measured with different concentrations of NaCl solutions. Further, a very high refractive resolution for the silver-based SPR sensor was found to be 2.207 × 10-7 RIU, which reaches the theoretical limit in the wavelength of 632.8 nm for a SPR sensor reported in the literature. Using a mixed SAM of 16-mercaptohexadecanoic acid (MHDA) and a MUD layer with a ratio of 1:10, this immunosensor for the rabbit immunoglobulin G (IgG) molecule with a limit of detection as low as 22.516 ng/mL was achieved.

Crosstalk-Free, Stretching-Insensitive Sensor Based on Arch-Bridge Architecture for Tactile Mapping with Parallel Addressing Strategy toward Million-Scale-Pixels Processing.

In the field of biomimetic electronics, flexible sensors with both high resolution and large size are attracting a lot of attention. However, attempts to increase the number of sensor pixels have been thwarted by the need for complex inner circuits and the resulting interferences with the output. Technological challenges, such as real-time spatiotemporal mapping and long-time reliability, must be resolved for large-scale sensor matrices. This paper reports a simple and robust sensor with an arch-bridge architecture (ABA) to address these challenges. The device, which consists of an anti-icing all-transparent material system, is fabricated by immobilizing ABA ionic arrays on predefined grooves on the substrate. It systematically integrates ABA structure-designing, resistance-position-sensing, and parallel-addressing logic, allowing for an improvement of three orders of magnitude in the scanning speed (million-scale pixels) without logical "diagnose confusion." In addition, it can withstand 100 000 stretching cycles without functional failure. It is also resistant to interferences from stretching. humidity, wet surfaces, and power lines. The proposed strategy is envisaged to serve as a general solution for high-density, large-area tactile sensors in various applications.

Improved Therapeutic Efficiency against Obesity through Transdermal Drug Delivery Using Microneedle Arrays.

In this paper, we prepared patches that were composed of a degradable microneedle (MN) array with a soft backing provided for the skin tissue. We then performed a transdermal delivery of anti-obesity drugs to evaluate the effectiveness of ß3 adrenergic receptor CL316243 in obesity treatment in overweight mice induced by a high-fat diet. Eighty male National Institutes of Health (NIH) mice were randomly divided into four obese groups or the control group. The obesity groups were given a high-fat diet for 15-18 weeks to establish an obese model. Afterward, the obese groups were divided into the following four groups: the control group, the unloaded MN group, the CL-316243 MN group, and the injection group. For the injection group, the group of mice was injected subcutaneously with CL316243 (1 mg/(kg·day)) for 15 days. Furthermore, the CL-316243 MN group was given a lower dose (0.1 mg/(kg·day)) for 15 days. After weighing the mice, we used Western blotting to detect the expression of uncoupling protein 1 (UCP1) in the adipose tissue around the mouse viscera. The results stated that the weight of the CL-316243 MN group and the injection group dropped, and the UCP1 protein expression of brown adipose tissue (BAT) significantly increased. The results demonstrated the ß3 adrenergic receptor agonist CL316243 could be carried into the body through MN, and the dose applied was considerably smaller than the injection dose. The reason for this may arise from the CL-316243 being delivered by MN arrays to subcutaneous adipose tissue more efficiently, with an even distribution, compared to that of the injection dose. This technique provides a new and feasible way to treat obesity more effectively.

Early changes of NLRP3 inflammasome activation after hypoxic-ischemic brain injury in neonatal rats.

The pathogenesis of neonatal hypoxic-ischemic (HI) brain injury may involve activation of the NOD-like receptor family pyrin domain-containing-3 (NLRP3) inflammasome and its downstream effectors, caspase-1 and interleukin (IL)-1ß. The start time of therapy is associated with adverse neurodevelopmental outcome following HI injury. We performed this study investigating early dynamic changes in NLRP3, caspase-1, and IL-1ß expression during the first 24 h following HI brain injury in an animal model, in order to optimize selection of treatment time after injury. Rats were randomized to an HI group (n=40) and sham group (n=40). Rats in the HI group were subjected to right common carotid artery ligation and then exposed to hypoxia (8% O2) for 2 h, and divided into 5 subgroups with 8 cases in each group at 5 postoperative time points (0, 4, 8, 12, 24 h). Brain injury during the first 24 h after surgery/hypoxia was evaluated by cranial ultrasonography. RT-PCR, western blot, and immunohistochemistry were applied to determine protein and mRNA expressions. In the HI group, ultrasonography revealed accelerated right vertebrobasilar artery flow at 4 h, enhanced brain parenchyma echogenicity at 24 h, and blood stealing from the vertebrobasilar artery at 24 h. In the HI group, immunohistochemistry demonstrated elevated expressions of NLRP3 and IL-1ß at 4, 8, 12, and 24 h and enhanced expression of caspase-1 at 8 and 12 h (all P < 0.01). Western blot and RT-PCR revealed that, compared with the sham group, the HI group exhibited elevated expression of NLRP3 at 4, 8, and 24 h, caspase-1 at 12 h, and IL-1ß at 8 h (all P < 0.05). In summary, the present results suggested that activation of NLRP3/caspase-1/IL-1ß signaling occurs within 4 h of HI brain injury in the neonatal rat.

Systematic investigation of intracellular trafficking behavior of one-dimensional alumina nanotubes.

Nanotube materials exhibit high drug loading capacity and controlled drug release properties, providing new opportunities for drug delivery. However, the intracellular trafficking paths of 1-dimensional (1D) nanostructured materials are poorly understood compared to their spherical counterparts, impeding the broad application of 1D materials as drug carriers. Here, we report the intracellular trafficking mechanism of nontoxic and biocompatible nanomaterials called anodic alumina nanotubes (AANTs), a model for 1D materials with a geometry that can be precisely engineered. The results indicated that AANTs enter the cells mainly by caveolin endocytosis and micropinocytosis and that cells use a novel macropinocytosis-late endosomes (LEs)-lysosomes route to transport AANTs. Moreover, liposomes (marked by DsRed-Rab18) are fully involved in the classical pathway of early endosomes (EEs)/LEs developing into lysosomes. The AANTs were delivered to the cells via two pathways: slow endocytosis recycling and GLUT4 exocytosis vesicles. The AANTs also induced intracellular autophagy and then degraded via the endolysosomal pathway. Blocking endolysosomal pathways using autophagy inhibitors prevented the degradation of AANTs through lysosomes. Our results add new insights into the pathways and mechanisms of intracellular trafficking of AANTs, and suggest that intracellular trafficking and lysosomal degradation are highly interdependent and important for efficient drug delivery, and should be evaluated together for drug carrier development.

[Effects of intradermal needling on core muscle stability in children with cerebral palsy: a clinical comparative study].

OBJECTIVE: To observe the effects of rehabilitation training (RT) combined with intradermal needling, RT combined with acupuncture and RT alone on core muscle stability in children with cerebral palsy, and to explore the superior therapy to improve core muscle stability in children with cerebral palsy. METHODS: A total of 120 children with cerebral palsy aged from 2 to 4 years old were randomly divided into a RT and intradermal needling group (group A), a RT and acupuncture group (group B) and a RT group (group C), 40 cases in each one. The patients in the group C were treated with kinesitherapy and core muscle stability training, once a day. Along with identical RT of group C, the patients in the group B were treated with acupuncture (once a day), while the patients in the group A were treated with intradermal needling at Yaoyangguan (GV 3), Mingmen (GV 4), Jiaji (EX-B 2, L2-L5), and 4-week treatment was taken as one course. The integrated electromyography (iEMG) of surface electromyography, root mean square (RMS) and mean power frequency (MPF) of erector spinae muscles, Berg balance scale as well as B area (siting), C area (climbing and kneeling), D area (standing) and E area (walking, running and jumping) of gross motor function measure (GMFM) were compared before and after 3-course treatment. RESULTS: ① Compared before treatment, the iEMG and RMS of erector spinae muscles in the group A and group B as well as MPF in the group A were all increased after treatment (all P<0.05); after treatment, all the electromyography indexes in the group A were higher than those in the group B and group C (all P<0.05); the RMS in the group B was higher than that in the group C (P<0.05). ② Compared before treatment, the Berg balance scale was all increased after treatment in the three groups (all P<0.05), and the scale in the group A was higher those that in the group B and group C (both P<0.05). ③ Compared before treatment, the B area and C area of GMFM in the three groups as well as D area in the group A and group B were all improved after treatment (all P<0.05); the B area, C area and D area in the group A and group B were higher than those in the group C (all P<0.05); the B area and C area in the group A were higher than those in the group B (both P<0.05). CONCLUSION: Based on RT, the intradermal needling could better improve core muscle stability and balance-motor ability in children with cerebral palsy, which is superior to regular acupuncture and RT alone.

Therapies for children with cerebral palsy: A Web of Science-based literature analysis.

OBJECTIVE: To identify global research trends in three therapies for children with cerebral palsy. DATA RETRIEVAL: We performed a bibliometric analysis of studies on therapies for children with cerebral palsy from 2002 to 2011 retrieved from Web of Science. INCLUSION CRITERIA: (a) peer-reviewed published articles on botulinum toxin, constraint-induced movement therapy, or acupuncture for children with cerebral palsy indexed in Web of Science; (b) original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items; and (c) publication between 2002 and 2011. EXCLUSION CRITERIA: (a) articles that required manual searching or telephone access; (b) documents that were not published in the public domain; and (c) a number of corrected papers from the total number of articles. MAIN OUTCOME MEASURES: (1) Number of publications on the three therapies; (2) annual publication output, distribution by journals, distribution by institution, and top-cited articles on botulinum toxin; (3) annual publication output, distribution by journal, distribution by institution, and top-cited articles on constraint-induced movement therapy; (4) annual publication, distribution by journal, distribution by institution, and top-cited articles on acupuncture. RESULTS: This analysis, based on Web of Science articles, identified several research trends in studies published over the past 10 years of three therapies for children with cerebral palsy. More articles on botulinum toxin for treating children with cerebral palsy were published than the articles regarding constraint-induced movement therapy or acupuncture. The numbers of publications increased over the 10-year study period. Most papers appeared in journals with a focus on neurology, such as Developmental Medicine and Child Neurology and Journal of Child Neurology. Research institutes publishing on botulinum toxin treatments for this population are mostly in the Netherlands, the United States of America, and Australia; those publishing on constraint-induced movement therapy are mostly in Australia and the United States of America; and those publishing on acupuncture are mostly in China, Sweden and the United States of America. CONCLUSION: Analysis of literature and research trends indicated that there was no one specific therapy to cure cerebral palsy. Further studies are still necessary.

[Effects of electroacupuncture combined with behavior therapy on intelligence and behavior of children of autism].

OBJECTIVE: To find out an effective therapy for autism. METHODS: Sixty children of autism were randomly divided into an electroacupuncture (EA) plus behavior therapy group and a behavior therapy group, 30 cases in each group. The patients in the two groups were treated with routine behavior, with EA at Baihui (GV 20), Sishencong (EX-HN 1), Shenting (GV 24), Benshen (GB 13), Yintang (EX-HN 3), Naohu (GV 17), Naokong (GB 19), Neiguan (PC 6) and scalp acupuncture at Speech Areas I, II, III added for the EA plus behavior therapy group. Their therapeutic effects were observed, and the picture and vocabulary scale (PPVT) and behavior ability were detected. RESULTS: The total effective rate was 86.7% in the EA plus behavior therapy group which was better than 56.7% of the behavior therapy group, and had significant enhancement in sensation, association, body, and ability of self-care (P < 0.05) and was better than the behavior therapy group in sensation, body and self-care factors, with no significantly improvement in the scores of PPVT in the two groups (P > 0.05). CONCLUSION: EA combined with behavior therapy can significantly improve clinical symptoms of autism, but does not improve intelligence.