[Determination of polybrominated diphenyl ethers in marine sediments by composite chromatography column purification-gas chromatography-negative chemical ionization-mass spectrometry].

Polybrominated diphenyl ethers (PBDEs) are used as additive flame retardants. Because they lack the ability to form chemical bonds, PBDEs can easily enter the sediment environment. The accurate qualitative and quantitative analysis of PBDEs in sediments is of great importance for the accurate assessment of PBDE pollution in this environment. Sediments contain many impurities. Therefore, PBDEs in sediment should be purified before analysis to reduce the matrix effect. A method based on gas chromatography-negative chemical ionization-mass spectrometry (GC-NCI/MS) was developed to determine 13 PBDEs in marine sediment samples using a column packed with deactivated silica gel, acidified silica gel, Florisil, and anhydrous sodium sulfate. Sediment samples were extracted by ultrasonication with a mixed solvent of n-hexane-dichloromethane (3∶1, v/v). After two cycles of ultrasonic extraction, the extract was purified by a composite chromatographic column and eluted with n-hexane-dichloromethane (3∶1, v/v). Thirteen PBDEs were determined by GC-NCI/MS in selected-ion monitoring (SIM) mode. The effects of different fillers, eluents, and elution volumes on the purification of PBDEs in the composite column were compared and analyzed, and the GC-NCI/MS analysis conditions were optimized. Three different packing columns were used to purify the sample extract. The first column was packed with 3 g of deactivated silica, 6 g of acidic silica, 3 g of deactivated silica, 3 g of Florisil, and 6 g of anhydrous sodium sulfate; the second column was packed with 3 g of Florisil, 3 g of deactivated silica, 6 g of acidic silica, 3 g of deactivated silica, and 6 g of anhydrous sodium sulfate; and the third column was packed with 3 g of deactivated silica, 6 g of acidified silica, 3 g of deactivated silica, and 6 g of anhydrous sodium sulfate. Among these columns, that packed with 3 g of deactivated silica, 6 g of acidic silica, 3 g of deactivated silica, 3 g of Florisil, and 6 g of anhydrous sodium sulfate showed the best purification effect. The 13 PBDEs showed good linearity in the mass concentration range of 0.1-20 µg/L with correlation coefficients (r2) greater than 0.995 (decabromodiphenyl oxide (BDE-209), r2>0.99). The limits of quantification (S/N=10) was 0.002-0.126 µg/kg. The average recoveries of the 13 PBDEs at three spiked levels of 0.2, 1.0, and 4.0 µg/kg were 85.3%-101.3%, 84.8%-113.6%, and 86.3%-94.7% with relative standard deviations of 4.4%-14.0%, 0.4%-4.9%, and 1.9%-6.6%, respectively. These findings indicate that the method has high sensitivity and accuracy as well as good precision. Finally, the method was applied to the analysis and detection of PBDEs in actual marine sediment samples. The results revealed that the sediment samples contained different contents of the 13 PBDEs, and high detection rates were obtained for lower-brominated PBDE homologs. The detection rate of bis(4-bromophenyl) ether (BDE-15) was 100%, and the detected content of BDE-209 was as high as 60.49 µg/kg. These results demonstrate that the developed method is suitable for the accurate qualitative and quantitative analysis of PBDEs in marine sediment samples.

Copper-mediated aerobic trifluoromethyltelluration of boronic acids with [Me4N][TeCF3].

A copper-mediated trifluoromethyltelluration of arylboronic acids with [Me4N][TeCF3] using air as an environmental friendly oxidant is presented. The reaction proceeded smoothly under mild conditions in the presence of Cu(OTf)2 and bipyridine to provide the corresponding trifluoromethyltellurated products in good yields. Vinylboronic acid and arylboronic acid pinacol ester were also suitable substrates in the conversion but the yields are low. This transformation featured simplicity, good functional group tolerance, and a wide range of substrates, allowing for a convenient access to various TeCF3-containing molecules, and represented the first Chan-Lam type trifluoromethyltelluration with the highly reactive [Me4N][TeCF3] salt.

Curvilinear soft electronics by micromolding of metal nanowires in capillaries.

Soft electronics using metal nanowires have attracted notable attention attributed to their high electrical conductivity and mechanical flexibility. However, high-resolution complex patterning of metal nanowires on curvilinear substrates remains a challenge. Here, a micromolding-based method is reported for scalable printing of metal nanowires, which enables complex and highly conductive patterns on soft curvilinear and uneven substrates with high resolution and uniformity. Printing resolution of 20 µm and conductivity of the printed patterns of ~6.3 × 106 S/m are achieved. Printing of grid structures with uniform thickness for transparent conductive electrodes (TCEs) and direct printing of pressure sensors on curved surfaces such as glove and contact lens are also realized. The printed hybrid soft TCEs and smart contact lens show promising applications in optoelectronic devices and personal health monitoring, respectively. This printing method can be extended to other nanomaterials for large-scale printing of high-performance soft electronics.

FOXC1 Negatively Regulates DKK1 Expression to Promote Gastric Cancer Cell Proliferation Through Activation of Wnt Signaling Pathway.

Gastric cancer (GC), characterized by uncontrolled growth, is a common malignant tumor of the digestive system. The Wnt signaling pathway plays an important role in the tumorigenesis and proliferation of GC. Many studies on this signaling pathway have focused on its intracellular regulatory mechanism, whereas little attention has been given to extracellular regulatory factors. Dickkopf-1 (Dkk1) is a secretory glycoprotein, and it can bind inhibit activation of the Wnt pathway. However, the regulation and mechanism of DKK1 in the proliferation of GC remain unclear. FOXC1 plays an important role in organ development and tumor growth, but its role in GC tumor growth remains unknown. In this study, we found that the FOXC1 is highly expressed in patients with GC and high expression of FOXC1 correlates to poor prognosis. In addition, we found that the Wnt signaling pathway in GC cells with high FOXC1 expression was strongly activated. FOXC1 negatively regulates DKK1 expression by binding to its promoter region, thereby promoting the activation of Wnt pathway. FOXC1 can also form a complex with unphosphorylated ß-catenin protein in the cytoplasm and then dissociates from ß-catenin in the nucleus, thereby promoting the entry of ß-catenin into the nucleus and regulating expression of c-MYC, which promotes the proliferation of GC cells. Our study not only reveals the function and mechanism of FOXC1 in GC, but also provides a potential target for clinic GC treatment.

Programmable soft electrothermal actuators based on free-form printing of the embedded heater.

In recent years, there has been an increasing interest in the research in soft actuators that exhibit complex programmable deformations. Soft electrothermal actuators use electricity as the stimulus to generate heat, and the mismatch between the thermal expansions of the two structural layers causes the actuator to bend. Complex programmable deformations of soft electrothermal actuators are difficult due to the limitations of the conventional fabrication methods. In this article, we report a new approach to fabricate soft electrothermal actuators, in which the resistive heater of the electrothermal actuator is directly printed using electrohydrodynamic (EHD) printing. The direct patterning capabilities of EHD printing allow the free-form design of the heater. By changing the design of the heating pattern on the actuator, different heat distributions can be achieved and utilized to realize complex programmable deformations, including uniform bending, customized bending, folding, and twisting. Finite element analysis (FEA) was used to validate the thermal distribution and deformation for different actuator designs. Lastly, several integrated demonstrations are presented, including complex structures obtained from folding, a two-degree-of-freedom soft robotic arm, and soft walkers.

Facile Approach to Fabricating Stretchable Organic Transistors with Laser-Patterned Ag Nanowire Electrodes.

Stretchable electronics are poised to revolutionize personal healthcare and robotics, where they enable distributed and conformal sensors. Transistors are fundamental building blocks of electronics, and there is a need to produce stretchable transistors using low-cost and scalable fabrication techniques. Here, we introduce a facile fabrication approach using laser patterning and transfer printing to achieve high-performance, solution-processed intrinsically stretchable organic thin-film transistors (OTFTs). The device consists of Ag nanowire (NW) electrodes, where the source and drain electrodes are patterned using laser ablation. The Ag NWs are then partially embedded in a poly(dimethylsiloxane) (PDMS) matrix. The electrodes are combined with a PDMS dielectric and polymer semiconductor, where the layers are individually transfer printed to complete the OTFT. Two polymer semiconductors, DPP-DTT and DPP-4T, are considered and show stable operation under the cyclic strain of 20 and 40%, respectively. The OTFTs maintain electrical performance by adopting a buckled structure after the first stretch-release cycle. The conformability and stretchability of the OTFT is also demonstrated by operating the transistor while adhered to a finger being flexed. The ability to pattern highly conductive Ag NW networks using laser ablation to pattern electrodes as well as interconnects provides a simple strategy to produce complex stretchable OTFT-based circuits.

Nanomaterial-Enabled Flexible and Stretchable Sensing Systems: Processing, Integration, and Applications.

Nanomaterial-enabled flexible and stretchable electronics have seen tremendous progress in recent years, evolving from single sensors to integrated sensing systems. Compared with nanomaterial-enabled sensors with a single function, integration of multiple sensors is conducive to comprehensive monitoring of personal health and environment, intelligent human-machine interfaces, and realistic imitation of human skin in robotics and prosthetics. Integration of sensors with other functional components promotes real-world applications of the sensing systems. Here, an overview of the design and integration strategies and manufacturing techniques for such sensing systems is given. Then, representative nanomaterial-enabled flexible and stretchable sensing systems are presented. Following that, representative applications in personal health, fitness tracking, electronic skins, artificial nervous systems, and human-machine interactions are provided. To conclude, perspectives on the challenges and opportunities in this burgeoning field are considered.

Electrohydrodynamic printing of silver nanowires for flexible and stretchable electronics.

A silver nanowire (AgNW) based conductor is a promising component for flexible and stretchable electronics. A wide range of flexible/stretchable devices using AgNW conductors has been demonstrated recently. High-resolution, high-throughput printing of AgNWs remains a critical challenge. Electrohydrodynamic (EHD) printing has been developed as a promising technique to print different materials on a variety of substrates with high resolution. Here, AgNW ink was developed for EHD printing. The printed features can be controlled by several parameters including AgNW concentration, ink viscosity, printing speed, stand-off distance, etc. With this method, AgNW patterns can be printed on a range of substrates, e.g. paper, polyethylene terephthalate (PET), glass, polydimethylsiloxane (PDMS), etc. First, AgNW samples on PDMS were characterized under bending and stretching. Then AgNW heaters and electrocardiogram (ECG) electrodes were fabricated to demonstrate the potential of this printing technique for AgNW-based flexible and stretchable devices.

Roles of hydroxyapatite allocation and microgroove dimension in promoting preosteoblastic cell functions on photocured polymer nanocomposites through nuclear distribution and alignment.

This study clarifies how hydroxyapatite (HA) allocation and microgroove dimension affect mouse preosteoblastic MC3T3-E1 cell functions on microgrooved substrates of polymer nanocomposites. Using replica molding from micromachined silicon wafer templates, we fabricated photocured poly(ε-caprolactone) triacrylate (PCLTA)/HA nanocomposite substrates with parallel microgrooves (two groove widths of 5 and 15 µm and one groove depth of 5 µm). Four types of microgrooved substrates were made: "homogeneous" ones of PCLTA and PCLTA/HA with uniform distribution and two "heterogeneous" laminated microgrooved substrates with HA only in the PCLTA matrix in the ridges or bottom. These substrates were used to regulate MC3T3-E1 cell attachment, proliferation, alignment, nuclear circularity and distribution, and mineralization. MC3T3-E1 cell attachment and proliferation were much higher on the microgrooved substrates of PCLTA/HA than on those of PCLTA, in particular, on the 5 µm wide microgrooved substrate with PCLTA/HA ridges and PCLTA bottom. The shape and distribution of MC3T3-E1 cytoskeleton and nuclei were altered by the substrate topography and HA allocation. For 5 µm wide heterogeneous microgrooved substrates with HA only in the ridges, MC3T3-E1 cells exhibited better spreading perpendicular to the microgrooves but tended to extend along the microgrooves containing HA in the bottom. The widest cells and the roundest/largest cell nuclei were observed on the heterogeneous substrate with PCLTA/HA ridges, while the narrowest cells with the best elongation were found on the homogeneous PCLTA/HA substrate. The trend in MC3T3-E1 cell mineralization on the substrates was consistent with that in cell/nuclear elongation. Osteocalcin mRNA expression was significantly higher on the PCLTA/HA substrates than on the PCLTA ones and also on the microgrooved substrates of PCLTA/HA than on the flat ones, regardless of the groove width of 5 or 15 µm.

Biodegradable photo-crosslinked polymer substrates with concentric microgrooves for regulating MC3T3-E1 cell behavior.

Both intrinsic material properties and topographical features are critical in influencing cell-biomaterial interactions. We present a systematic investigation of regulating mouse pre-osteoblastic MC3T3-E1 cell behavior on biodegradable polymer substrates with distinct mechanical properties and concentric microgrooves. The precursors for fabricating substrates used here were two poly(ϵ-caprolactone) triacrylates (PCLTAs) synthesized from poly(ϵ-caprolactone) triols with molecular weights of ∼7000 and ∼10000 g mol(-1) . These two PCLTAs were photo-crosslinked into PCL networks with distinct thermal, rheological, and mechanical properties at physiological temperature because of their different crystallinities and melting temperatures. Microgrooved substrates with four groove widths of 7.5, 16.1, 44.2, and 91.2 µm and three groove depths of 0.2, 1, and 10 µm were prepared through replica molding, i.e., photo-crosslinking PCLTA on micro-fabricated silicon wafers with pre-designed concentric groove patterns. MC3T3-E1 cell attachment and proliferation could be better supported by the stiffer substrates while not significantly influenced by the microgrooves. Microgroove dimensions could regulate MC3T3-E1 cell alignment, nuclear shape and distribution, mineralization, and gene expression. Among the microgrooves with a fixed depth of 10 µm, the smallest width of 7.5 µm could align and elongate the cytoskeleton and nuclei most efficiently. Strikingly, higher mineral deposition and upregulation of osteocalcin gene expression were found in the narrower microgrooves when the groove depth was 10 µm.

Photocured biodegradable polymer substrates of varying stiffness and microgroove dimensions for promoting nerve cell guidance and differentiation.

Photocross-linkable and biodegradable polymers have great promise in fabricating nerve conduits for guiding axonal growth in peripheral nerve regeneration. Here, we photocross-linked two poly(ε-caprolactone) triacrylates (PCLTAs) with number-average molecular weights of ~7000 and ~10,000 g mol(-1) into substrates with parallel microgrooves. Cross-linked PCLTA7k was amorphous and soft, while cross-linked PCLTA10k was semicrystalline with a stiffer surface. We employed different dimensions of interests for the parallel microgrooves, that is, groove widths of 5, 15, 45, and 90 µm and groove depths of 0.4, 1, 5, and 12 µm. The behaviors of rat Schwann cell precursor line (SpL201) cells with the glial nature and pheochromocytoma (PC12) cells with the neuronal nature were studied on these microgrooved substrates, showing distinct preference to the substrates with different mechanical properties. We found different threshold sensitivities of the two nerve cell types to topographical features when their cytoskeleton and nuclei were altered by varying the groove depth and width. Almost all of the cells were aligned in the narrowest and deepest microgrooves or around the edge of microgrooves. Oriented SpL201 cell movement had a higher motility as compared to unaligned ones. After forskolin treatment, SpL201 cells demonstrated significantly upregulated S-100 and O4 on stiffer substrates or narrower microgrooves, suggesting more differentiation toward early Schwann cells (SCs). PC12 neurites were oriented with enhanced extension in narrower microgrooves. The present results not only improve our fundamental understanding on nerve cell-substrate interactions, but also offer useful conduit materials and appropriate feature dimensions to foster guidance for axonal growth in peripheral nerve regeneration.

High-precision flexible fabrication of tissue engineering scaffolds using distinct polymers.

Three-dimensional porous structures using biodegradable materials with excellent biocompatibility are critically important for tissue engineering applications. We present a multi-nozzle-based versatile deposition approach to flexibly construct porous tissue engineering scaffolds using distinct polymeric biomaterials such as thermoplastic and photo-crosslinkable polymers. We first describe the development of the deposition system and fabrication of scaffolds from two types of biodegradable polymers using this system. The thermoplastic sample is semi-crystalline poly(ε-caprolactone) (PCL) that can be processed at a temperature higher than its melting point and solidifies at room temperature. The photo-crosslinkable one is polypropylene fumarate (PPF) that has to be dissolved in a reactive solvent as a resin for being cured into solid structures. Besides the direct fabrication of thermoplastic PCL scaffolds, we specifically develop a layer molding approach for the fabrication of crosslinkable polymers, which traditionally can only be fabricated by stereolithography. In this approach, a thermoplastic supporting material (paraffin wax) is first deposited to make a mold for each specific layer, and then PPF is deposited on demand to fill the mold and cured by the UV light. The supporting material can be removed to produce a porous scaffold of crosslinked PPF. Both PCL and crosslinked PPF scaffolds fabricated using the developed system have been characterized in terms of compressive mechanical properties, morphology, pore size and porosity. Mouse MC3T3-E1 pre-osteoblastic cell studies on the fabricated scaffolds have been performed to demonstrate their capability of supporting cell proliferation and ingrowth, aiming for bone tissue engineering applications.

High-rate tunable ultrasonic force regulated nanomachining lithography with an atomic force microscope.

This paper describes a high-rate tunable nanomachining-based nanolithography technique using an atomic force microscope (AFM). Controlled vibration between the cantilever tip and the sample is introduced to increase the lithographical speed and controllability of the nanomachining process. In this approach, an ultrasonic z vibration of the sample and the resulting ultrasonic force from the nonlinear force-distance interaction between the sample and the cantilever tip are utilized to regulate fabrication depth. A high frequency in-plane circular vibration is introduced between the tip and the sample to control the width of the fabricated features, and to improve the speed of nanolithography. Features (e.g. slots) with dimensions spanning from tens of nanometers to hundreds of nanometers are fabricated in one scan. A lithography speed of tens of microns per second can be achieved, which is significantly higher than other known mechanical-modification-based nanolithography methods. The patterns, that are machined on a thin PMMA film, are transferred to silicon substrate through a reactive ion etching process, which provides a cost-effective tunable approach for the fabrication of nanostructures.

Neuroprotective effect of erythropoietin-loaded composite microspheres on retinal ganglion cells in rats.

This study explored a sustained neuroprotective erythropoietin (EPO) loaded composite microspheres system on injured retinal ganglion cells (RGC). The EPO was first loaded into dextran microparticles to keep its bioactivity using a novel "aqueous-aqueous emulsion" technique. The microspheres were finally formed by encapsulating the microparticles into Poly (DL-lactide-co-glycolide)/Poly (DL-lactide) (PLGA/PLA). A single dose of microspheres was intraperitoneally administrated on the optic nerve crush of rats and compared with multiple doses of EPO solution to investigate the long acting effect of microspheres on RGC. The results demonstrated that the release of microspheres could last for at least 60 days in an in vitro study. The animal experiments showed a similar neuroprotective effect between the single dose microspheres and the multiple doses of EPO solution. So we can draw a conclusion that the EPO-loaded PLGA/PLA microspheres were feasible for neurodegeneration diseases in the retina and central nervous system (CNS).

High bandwidth control of precision motion instrumentation.

This article presents a high-bandwidth control design suitable for precision motion instrumentation. Iterative learning control (ILC), a feedforward technique that uses previous iterations of the desired trajectory, is used to leverage the repetition that occurs in many tasks, such as raster scanning in microscopy. Two ILC designs are presented. The first design uses the motion system dynamic model to maximize bandwidth. The second design uses a time-varying bandwidth that is particularly useful for nonsmooth trajectories such as raster scanning. Both designs are applied to a multiaxis piezoelectric-actuated flexure system and evaluated on a nonsmooth trajectory. The ILC designs demonstrate significant bandwidth and precision improvements over the feedback controller, and the ability to achieve precision motion control at frequencies higher than multiple system resonances.