[Effects of tumor necrosis factor-alpha/extracellular signal-regulated kinase pathway on migration ability of HaCaT cells and full-thickness skin defects in mice].

Objective: To investigate the effects of tumor necrosis factor-alpha (TNF-α)/extracellular signal-regulated kinase (ERK) pathway on the migration ability of HaCaT cells and full-thickness skin defects in mice. Methods: The experimental research method was adopted. According to the random number table (the same below), HaCaT cells were divided into the normal oxygen group and the hypoxia group cultured under hypoxia (with oxygen volume fraction of 1%, the same below) condition. After 24 hours of culture, the significantly differentially expressed genes between the 2 groups were screened using the microarray confidence analysis software SAM4.01. The significance of the number of each gene in the signaling pathway was analyzed through the Kyoto encyclopedia of genes and genomes to screen the significantly differentially signaling pathways (n=3). HaCaT cells were cultured for 0 (immediately), 3, 6, 12, and 24 h under hypoxia condition. The secretion level of TNF-α was detected by enzyme-linked immunosorbent assay (ELISA), and the number of samples was 5. HaCaT cells were divided into normal oxygen group, hypoxia alone group, and hypoxia+inhibitor group cultured with FR180204 (an ERK inhibitor) and under hypoxia condition. The cells were cultured for 3, 6, 12, and 24 h. The migration ability of the cells was detected by scratch test (n=12). The expressions of phosphorylated nuclear factor kappa B (p-NF-κB), phosphorylated p38 (p-p38), phosphorylated ERK1/2 (p-ERK1/2), N-cadherin, and E-cadherin in HaCaT cells were detected by Western blotting under hypoxic condition for 0, 3, 6, 12, and 24 h (n=3). Sixty-four BALB/c male mice aged 6 to 8 weeks were used to make a full-thickness skin defect wound model on the dorsum of the mice. The mice were divided into the blank control group and the inhibitor group treated with FR180204, with 32 mice in each group being treated accordingly. On post injury day (PID) 0, 3, 6, 9, 12, and 15, the wound conditions of mice were observed and the healing rate was calculated (n=8). On PID 1, 3, 6, and 15, hematoxylin-eosin staining was used to observe neovascularization, inflammatory cell infiltration, and epidermal regeneration on wound, Masson staining was used to observe collagen deposition on wound, the expressions of p-NF-κB, p-p38, p-ERK12, N-cadherin, and E-cadherin in wound tissue were detected by Western blotting (n=6), the number of Ki67 positive cells and the absorbance value of vascular endothelial growth factor (VEGF) were detected by immunohistochemistry (n=5), the protein expressions of interleukin 6 (IL-6), IL-10, IL-1ß, and CCL20 in wound tissue were detected by ELISA (n=6). Data were statistically analyzed with one-way analysis of variance, analysis of variance for repeated measurement, factorial design analysis of variance, Tukey test, least significant difference test, and independent sample t test. Results: After 24 hours of culture, compared with normal oxygen group, 7 667 genes were up-regulated and 7 174 genes were down-regulated in cells in hypoxic group. Among the above differentially expressed genes, the TNF-α signaling pathway had significant change (P<0.05) with large number of genes. Under hypoxia condition, the expression of TNF-α at 24 h of cell culture was (11.1±2.1) pg/mL, which was significantly higher than (1.9±0.3) pg/mL at 0 h (P<0.05). Compared with normal oxygen group, the migration ability of cells in hypoxia alone group was significantly enhanced at 6, 12, and 24 h of cell culture (with t values of 2.27, 4.65, and 4.67, respectively, P<0.05). Compared with hypoxia alone group, the migration ability of cells in hypoxia+inhibitor group was significantly decreased at 3, 6, 12, and 24 h of cell culture (with t values of 2.43, 3.06, 4.62, and 8.14, respectively, P<0.05). Under hypoxia condition, the expressions of p-NF-κB, p-ERK1/2, and N-cadherin were increased significantly at 12 and 24 h of cell culture compared with 0 h of culture (P<0.05), the expression of p-p38 was significantly increased at 3, 6, 12, and 24 h of cell culture (P<0.05), the expression of E-cadherin was significantly decreased at 6, 12, and 24 h of cell culture (P<0.05), the expression of p-ERK1/2, p-NF-κB, and E-cadherin was time-dependent. Compared with blank control group, on PID 3, 6, 9, 12, and 15, the wound healing rate of mice in inhibitor group was significantly decreased (P<0.05); there were more inflammatory cell infiltration around the wound edge of mice in inhibitor group on PID 3, 6, and 15, especially on PID 15, a large number of tissue necrosis and discontinuous new epidermal layer were observed on the wound surface, and collagen synthesis and new blood vessels were reduced; the expression of p-NF-κB in the wound of mice in inhibitor group was significantly decreased on PID 3 and 6 (with t values of 3.26 and 4.26, respectively, P<0.05) but significantly increased on PID 15 (t=3.25, P<0.05), the expressions of p-p38 and N-cadherin were significantly decreased on PID 1, 3, and 6 (with t values of 4.89, 2.98, 3.98, 9.51, 11.69, and 4.10, respectively, P<0.05), the expression of p-ERK1/2 was significantly decreased on PID 1, 3, 6, and 15 (with t values of 26.69, 3.63, 5.12, and 5.14, respectively, P<0.05), the expression of E-cadherin was significantly decreased on PID 1 (t=20.67, P<0.05) but significantly increased on PID 6 (t=2.90, P<0.05); the number of Ki67 positive cells and absorbance value of VEGF of wound in inhibitor group were significantly decreased on PID 3, 6, and 15 (with t values of 4.20, 7.35, 3.34, 4.14, 3.20, and 3.73, respectively, P<0.05); the expression of IL-10 in the wound tissue of the inhibitor group was significantly decreased on PID 6 (t=2.92, P<0.05), the expression of IL-6 was significantly increased on PID 6 (t=2.73, P<0.05), the expression of IL-1ß was significantly increased on PID 15 (t=3.46, P<0.05), and CCL20 expression levels were significantly decreased on PID 1 and 6 (with t values of 3.96 and 2.63, respectively, P<0.05) but significantly increased on PID 15 (t=3.68, P<0.05). Conclusions: The TNF-α/ERK pathway can promote the migration of HaCaT cells, and regulate the healing of full-thickness skin defect wounds in mice by affecting the expression of inflammatory cytokines and chemokines.

Man-made rotary nanomotors: a review of recent developments.

The development of rotary nanomotors is an essential step towards intelligent nanomachines and nanorobots. In this article, we review the concept, design, working mechanisms, and applications of state-of-the-art rotary nanomotors made from synthetic nanoentities. The rotary nanomotors are categorized according to the energy sources employed to drive the rotary motion, including biochemical, optical, magnetic, and electric fields. The unique advantages and limitations for each type of rotary nanomachines are discussed. The advances of rotary nanomotors is pivotal for realizing dream nanomachines for myriad applications including microfluidics, biodiagnosis, nano-surgery, and biosubstance delivery.

Ultra-durable rotary micromotors assembled from nanoentities by electric fields.

Recently, we reported an innovative type of micromotors consisting of nanowires as rotors and patterned Au/Ni/Cr nanodisks as bearings. The dimensions of micromotors were less than 1 µm, and could continuously rotate for 15 hours over 240 000 cycles. To understand the limitation of their lifetime, we systematically investigated the rotation dynamics by analytical modeling and determined the time-dependent torques and forces involved in the rotation. From the forces and torques, the extent of wear of micromotors was successfully derived, which agreed well with the experimental characterization. The results also proved that the frictional force linearly increases with the loading in such rotary nanodevices operating in suspension, consistent with the prediction of the non-adhesive multi-asperity friction theory. With these understandings, we enhanced the design of micromotors and achieved an operation lifetime of 80 hours and over 1.1 million total rotation cycles. This research, shedding new light on the frictional mechanism of recently reported nanowire micromotors with demonstration of the most durable rotary nanomechanical devices of similar dimensions to the best of our knowledge, can be inspiring for innovative design of future nanomechanical devices with ultra-long lifetime for practical applications.

Recent Progress on Man-Made Inorganic Nanomachines.

The successful development of nanoscale machinery, which can operate with high controllability, high precision, long lifetimes, and tunable driving powers, is pivotal for the realization of future intelligent nanorobots, nanofactories, and advanced biomedical devices. However, the development of nanomachines remains one of the most difficult research areas, largely due to the grand challenges in fabrication of devices with complex components and actuation with desired efficiency, precision, lifetime, and/or environmental friendliness. In this work, the cutting-edge efforts toward fabricating and actuating various types of nanomachines and their applications are reviewed, with a special focus on nanomotors made from inorganic nanoscale building blocks, which are introduced according to the employed actuation mechanism. The unique characteristics and obstacles for each type of nanomachine are discussed, and perspectives and challenges of this exciting field are presented.

Microfluidic channels with ultralow-loss waveguide crossings for various chip-integrated photonic sensors.

Traditional silicon waveguides are defined by waveguide trenches on either side of the high-index silicon core that leads to fluid leakage orifices for over-layed microfluidic channels. Closing the orifices needs additional fabrication steps which may include oxide deposition and planarization. We experimentally demonstrated a new type of microfluidic channel design with ultralow-loss waveguide crossings (0.00248 dB per crossings). The waveguide crossings and all other on-chip passive-waveguide components are fabricated in one step with no additional planarization steps which eliminates any orifices and leads to leak-free fluid flow. Such designs are applicable in all optical-waveguide-based sensing applications where the analyte must be flowed over the sensor. The new channel design was demonstrated in a L55 photonic crystal sensor operating between 1540 and 1580 nm.

Location deterministic biosensing from quantum-dot-nanowire assemblies.

Semiconductor quantum dots (QDs) with high fluorescent brightness, stability, and tunable sizes, have received considerable interest for imaging, sensing, and delivery of biomolecules. In this research, we demonstrate location deterministic biochemical detection from arrays of QD-nanowire hybrid assemblies. QDs with diameters less than 10 nm are manipulated and precisely positioned on the tips of the assembled Gold (Au) nanowires. The manipulation mechanisms are quantitatively understood as the synergetic effects of dielectrophoretic (DEP) and alternating current electroosmosis (ACEO) due to AC electric fields. The QD-nanowire hybrid sensors operate uniquely by concentrating bioanalytes to QDs on the tips of nanowires before detection, offering much enhanced efficiency and sensitivity, in addition to the position-predictable rationality. This research could result in advances in QD-based biomedical detection and inspires an innovative approach for fabricating various QD-based nanodevices.

Ultrahigh-speed rotating nanoelectromechanical system devices assembled from nanoscale building blocks.

The development of rotary nanomotors is crucial for advancing nanoelectromechanical system technology. In this work, we report design, assembly and rotation of ordered arrays of nanomotors. The nanomotors are bottom-up assembled from nanoscale building blocks with nanowires as rotors, patterned nanomagnets as bearings and quadrupole microelectrodes as stators. Arrays of nanomotors rotate with controlled angle, speed (over 18,000 r.p.m.), and chirality by electric fields. Using analytical modelling, we reveal the fundamental nanoscale electrical, mechanical and magnetic interactions in the nanomotor system, which excellently agrees with experimental results and provides critical understanding for designing metallic nanoelectromechanical systems. The nanomotors can be continuously rotated for 15 h over 240,000 cycles. They are applied for controlled biochemical release and demonstrate releasing rate of biochemicals on nanoparticles that can be precisely tuned by mechanical rotations. The innovations reported in this research, from concept, design and actuation to application, are relevant to nanoelectromechanical system, nanomedicine, microfluidics and lab-on-a-chip architectures.

Electric-Field Enhanced Molecule Detection in Suspension on Assembled Plasmonic Arrays by Raman Spectroscopy.

One of the greatest challenges in surface enhanced Raman scattering (SERS) sensing is to detect biochemicals directly from suspension with ultrasensitivity. In this work, we employed strategically designed longitudinal nanocapsule structures with uniformly surface distributed Ag nanoparticles (Ag NPs) to dually focus and enhance SERS sensitivity of biochemicals in suspension assisted with electric fields. By tuning the reaction conditions, Ag NPs were synthesized and uniformly grown with optimized sizes and junctions on the surface of nanocapsules for well reproducible detection. The Ag NPs can further concentrate molecules from suspension due to induced electrokinetic effects in electric fields. As a result, the signals of Nile blue molecules can be enhanced by 34.4±3.1% at optimal alternating current (AC) frequencies and voltages compared to that without electric fields. This work demonstrates the dual roles of a new type of plasmonic NPs for molecule concentration and detection, which could inspire new Raman sensing devices for applications in microfluidics.

One-Step Hydrothermal Synthesis of Comb-Like ZnO Nanostructures.

Zinc Oxide (ZnO) nano-superstructures (NSSs) have attracted intense research interests due to their large surface areas and unique properties. In this work, we report an original approach to synthesize ZnO NSSs in a one-step manner with a hydrothermal method. The crystalline structures and growth mechanism can be understood by surface energy calculations. The reaction kinetics was investigated for the control of the morphology of ZnO NSSs. The critical role of the morphology of Au catalysts in the synthesis of ZnO nanostructures has been demonstrated. Such ZnO NSSs can be fabricated on various rigid and flexible substrates for applications in electronics, solar cells and piezoelectric devices.

Ordered arrays of Raman nanosensors for ultrasensitive and location predictable biochemical detection.

Surface enhanced Raman scattering (SERS) is sensitive enough for single-molecule biochemical detection, but it is extremely difficult to obtain a large number of SERS hotspots for sensitive and reproducible detection. It is even more challenging to assemble the hotspots at designated positions for location predictable sensing. Here, we report an original strategy for the synthesis, manipulation, and assembling of plasmonic nanocapsule SERS sensors for high-sensitivity biochemical detection at predictable locations.

Guided-mode-resonance-coupled plasmonic-active SiO(2) nanotubes for surface enhanced Raman spectroscopy.

We demonstrate a surface enhanced Raman scattering (SERS) substrate by integrating plasmonic-active SiO(2) nanotubes into Si(3)N(4) gratings. First, the dielectric grating that is working under guided mode resonance (GMR) provides enhanced electric field for localized surface plasmon polaritons on the surface of metallic nanoparticles. Second, we use SiO(2) nanotubes with densely assembled silver nanoparticles to provide a large amount of "hot spots" without significantly damping the GMR mode of the grating. Experimental measurement on Rhodamine-6G shows a constant enhancement factor of 8 ∼ 10 in addition to the existing SERS effect across the entire surface of the SiO(2) nanotubes.

Electronic properties of nanoentities revealed by electrically driven rotation.

Direct electric measurement via small contacting pads on individual quasi-one-dimensional nanoentities, such as nanowires and carbon nanotubes, are usually required to access its electronic properties. We show in this work that 1D nanoentities in suspension can be driven to rotation by AC electric fields. The chirality of the resultantrotation unambiguously reveals whether the nanoentities are metal, semiconductor, or insulator due to the dependence of the Clausius-Mossotti factor on the material conductivity and frequency. This contactless method provides rapid and parallel identification of the electrical characteristics of 1D nanoentities.

Electric Tweezers.

Electric tweezers utilize DC and AC electric fields through voltages applied on patterned electrodes to manipulate nanoentities suspended in a liquid. Nanowires with a large aspect ratio are particularly suitable for use in electric tweezers for patterning, assembling, and manipulation. Despite operating in the regime of extremely small particle Reynolds number (of order 10-5), electric tweezers can manipulate nanowires with high precision to follow any prescribed trajectory, to rotate nanowires with controlled chirality, angular velocity and rotation angle, and to assemble nanowires to fabricate nanoelectromechanical system (NEMS) devices such as nanomotors and nano-oscillators. Electric tweezers have also been used to transport in a highly controlled manner drug-carrying functionalized nanowires for cell-specific drug delivery.

Wear properties of nano-Al2O3/UHMWPE composites irradiated by gamma ray against a CoCrMo alloy.

Nano-Al(2)O(3)/ultra-high molecular weight polyethylene (UHMWPE) composites were prepared by hot pressing and then radiated by a gamma ray in doses of 120 kGy, 250 kGy and 500 kGy. The hardness of the composites was tested. The friction and wear properties against a CoCrMo alloy were also tested on a knee simulator under physiological saline solution lubrication. The morphologies of worn surfaces were examined under an optical microscope. The structure of the sample was analyzed by IR and XRD tests. The results showed that the wear rate of UHMWPE decreased when filled with a proper amount of nano-Al(2)O(3), and with an increment of the radiation dose of gamma rays. It was found that filling nano-Al(2)O(3) into UHMWPE can inhibit the effect of oxidation during the radiation procedure.

Indoor air pollution in four cities in China.

The study reports the investigation of indoor air pollution carried out in four cities in China (Chengde, Shanghai, Shenyang and Wuhan). The concentrations of RP, SO2, CO and NO2 were measured in kitchens and bedrooms, both in summer and in winter. The results showed that indoor air pollution, as measured by RP, SO2, CO, was heavy when coal was used as domestic fuel. This was particularly severe in winter. For example, the concentrations of SO2 in homes with coal stoves were more than 10 times higher than those in homes with gas or LPG in Shanghai. The concentrations of pollutants in kitchens were higher than those in bedrooms. The source of pollutants was fuel combustion from kitchen. The highest concentrations in kitchen could reach 665 micrograms/m3 (RP), 860 micrograms/m3 (SO2) and 14.07 mg/m3 (CO). The concentrations in bedrooms were up to 270 micrograms/m3, 502 micrograms/m3, and 13.67mg/m3, respectively.