The culture of bone marrow derived mesenchymal stem cells (MSCs), as well as the control of its differentiation toward different tissue lineage, is a very important part of tissue engineering, where ...cells are combined with artificial scaffold to regenerate tissues. Graphene (G) and graphene oxide (GO) sheets are soft membranes with high in-plane stiffness and can potentially serve as a biocompatible, transferable, and implantable platform for stem cell culture. While the healthy proliferation of stem cells on various carbon platforms has been demonstrated, the chemical role of G and GO, if any, in guiding uncommitted stem cells toward differentiated cells is not known. Herein, we report that the strong noncovalent binding abilities of G allow it to act as a preconcentration platform for osteogenic inducers, which accelerate MSCs growing on it toward the osteogenic lineage. The molecular origin of accelerated differentation is investigated by studying the binding abilities of G and GO toward different growth agents. Interestingly, differentiation to adipocytes is greatly suppressed on G because insulin, which is a key regulator for the synthesis of fatty acids, is denatured upon π–π adsorption on G; in contrast, GO does not interfere with adipogenesis due to electrostatic binding with insulin. The different binding interactions and their subsequent influence on stem cell growth and differentiation are ascribed to different degrees of π–π stacking and electrostatic and hydrogen bonding mediated by G and GO.
BACKGROUND
Peripheral natural killer (pNK) and uterine NK (uNK) cells have been associated with reproductive failure. We systematically reviewed the literature to assess whether numbers or activity ...of pNK or uNK cells predicted subsequent pregnancy and outcome.
METHODS
We searched the electronic MEDLINE database from 1950 to April 2010 for relevant publications by using MeSH terms ‘natural killer cells’, ‘reproduction’ and ‘pregnancy complications’. We included studies that measured pre-pregnancy pNK and uNK cell numbers or activity in women with recurrent miscarriage (RM) or infertility, and reported subsequent pregnancy outcomes of miscarriage or failure to conceive after assisted reproductive technology (ART).
RESULTS
The search identified 783 publications and 12 fulfilled the inclusion criteria. There were too few women entered into the observational studies to assess whether high pNK cell percentages or activity predicted subsequent miscarriage in women with idiopathic RM (numbers: n = 32, OR 17, 95% CI 0.82–350.6, activity: n = 92, OR 2.51, 95% CI 0.16–40.29), or implantation failure (n = 203, OR 1.35, 95% CI 0.28–6.46), or miscarriage in infertile women after ART (n = 79, OR 2.48, 95% CI 0.50–12.32). Similarly, the studies of uNK cells were not large enough to assess whether abnormal uNK cell density predicted subsequent miscarriage in women with idiopathic RM (n = 72, OR 1.33, 95% CI 0.16–11.11). None of the uNK cell studies in women with infertility reported pregnancy outcomes dichotomized for uNK cell numbers.
CONCLUSIONS
The prognostic value of measuring pNK or uNK cell parameters remains uncertain. More studies are needed to confirm or refute the role of NK cell assessments as a predictive test for screening women who may benefit from immunotherapy.
A Nationwide Nitrogen Deposition Monitoring Network (NNDMN) containing 43 monitoring sites was established in China to measure gaseous NH3, NO2, and HNO3 and particulate NH4+ and NO3− in air and/or ...precipitation from 2010 to 2014. Wet/bulk deposition fluxes of Nr species were collected by precipitation gauge method and measured by continuous-flow analyzer; dry deposition fluxes were estimated using airborne concentration measurements and inferential models. Our observations reveal large spatial variations of atmospheric Nr concentrations and dry and wet/bulk Nr deposition. On a national basis, the annual average concentrations (1.3–47.0 μg N m−3) and dry plus wet/bulk deposition fluxes (2.9–83.3 kg N ha−1 yr−1) of inorganic Nr species are ranked by land use as urban > rural > background sites and by regions as north China > southeast China > southwest China > northeast China > northwest China > Tibetan Plateau, reflecting the impact of anthropogenic Nr emission. Average dry and wet/bulk N deposition fluxes were 20.6 ± 11.2 (mean ± standard deviation) and 19.3 ± 9.2 kg N ha−1 yr−1 across China, with reduced N deposition dominating both dry and wet/bulk deposition. Our results suggest atmospheric dry N deposition is equally important to wet/bulk N deposition at the national scale. Therefore, both deposition forms should be included when considering the impacts of N deposition on environment and ecosystem health.
Free vibration of non-uniform functionally graded beams is analyzed via the Timoshenko beam theory. Bending stiffness and distributed mass density are assumed to obey a unified exponential law. For ...various boundary conditions, exact frequency equations are derived in closed form. These frequency equations can reduce to those for classical Timoshenko beams if the gradient index disappears. Moreover, the frequency equations of exponentially graded Rayleigh, shear, and Euler–Bernoulli beams can be obtained as special cases of the present. The gradient index has a strong influence on the natural frequencies. For Timoshenko beams, there exist two critical frequencies depending on the gradient index. Harmonic vibration cannot be excited for frequencies less than the lower critical frequency. The obtained results can serve as a benchmark for examining the accuracy of numerical frequencies based on other approaches for analyzing transverse vibration of non-uniform axially graded Timoshenko beams. The results also apply to bending vibration of rectangular Timoshenko beams with constant thickness and exponentially decaying/amplifying width.
•Free vibration of functionally graded Timoshenko beams is analyzed.•Exact frequency equations of exponentially graded Timoshenko beams are obtained.•Effect of end constraints of functionally graded Timoshenko beams is examined.•Natural frequencies depend on the gradient index and admit jump property.•Natural frequencies for graded beams using Euler–Bernoulli, shear, Rayleigh, and Timoshenko theories are compared.
Most deaths from cancer are explained by metastasis, and yet large-scale metastasis research has been impractical owing to the complexity of in vivo models. Here we introduce an in vivo barcoding ...strategy that is capable of determining the metastatic potential of human cancer cell lines in mouse xenografts at scale. We validated the robustness, scalability and reproducibility of the method and applied it to 500 cell lines
spanning 21 types of solid tumour. We created a first-generation metastasis map (MetMap) that reveals organ-specific patterns of metastasis, enabling these patterns to be associated with clinical and genomic features. We demonstrate the utility of MetMap by investigating the molecular basis of breast cancers capable of metastasizing to the brain-a principal cause of death in patients with this type of cancer. Breast cancers capable of metastasizing to the brain showed evidence of altered lipid metabolism. Perturbation of lipid metabolism in these cells curbed brain metastasis development, suggesting a therapeutic strategy to combat the disease and demonstrating the utility of MetMap as a resource to support metastasis research.
Biosensors with high sensitivity and short time-to-result that are capable of detecting biomarkers in body fluids such as serum are an important prerequisite for early diagnostics in modern ...healthcare provision. Here, we report the development of an electrochemical impedance-based sensor for the detection in serum of human interleukin-8 (IL-8), a pro-angiogenic chemokine implicated in a wide range of inflammatory diseases. The sensor employs a small and robust synthetic non-antibody capture protein based on a cystatin scaffold that displays high affinity for human IL-8 with a KD of 35±10nM and excellent ligand specificity. The change in the phase of the electrochemical impedance from the serum baseline, ∆θ(ƒ), measured at 0.1Hz, was used as the measure for quantifying IL-8 concentration in the fluid. Optimal sensor signal was observed after 15min incubation, and the sensor exhibited a linear response versus logarithm of IL-8 concentration from 900fg/ml to 900ng/ml. A detection limit of around 90fg/ml, which is significantly lower than the basal clinical levels of 5–10pg/ml, was observed. Our results are significant for the development of point-of-care and early diagnostics where high sensitivity and short time-to-results are essential.
•A label-free electrochemical impedance-based sensor for the detection of human interleukin-8 (IL-8) in full serum was developed.•Detection limit of 90fg/ml and time-to-result of 15min was found.•A large dynamic range of the sensor was observed, with sensor response linear vs logarithm of IL-8 concentration from 900fg/ml to 900ng/ml.•The sensor employs a small and robust synthetic non-antibody capture protein, with high stability and excellent ligand specificity.•Findings are particularly relevant for the development of point-of-care and early diagnosis sensors where high sensitivity and short time-to-results are essential.
Static magnetic stimulation (SMS) is a form of non-invasive brain stimulation that alters neural activity and induces neural plasticity that outlasts the period of stimulation. This can modify ...corticospinal excitability or motor behaviours, suggesting that SMS may alter the intrinsic excitability of neurons. In mammalian neurons, the axon initial segment (AIS) is the site of action potential initiation and undergoes structural plasticity (changes in length and position from the soma) as a homeostatic mechanism to counteract chronic changes in neuronal activity. We investigated whether the chronic application of SMS (6 and 48 h, 0.5 T) induces structural AIS plasticity in postnatally derived primary cortical neurons. Following 6 h of SMS, we observed a shortening in mean AIS length compared to control, that persisted 24 h post stimulation. In contrast, 48 h of SMS induced an immediate distal shift that persisted 24 h post-stimulation. Pharmacological blockade of voltage gated L/T-type calcium channels during stimulation did not prevent SMS-induced AIS structural plasticity. Our findings provide the foundation to expand the use of chronic SMS as a non-invasive method to promote AIS plasticity.
A humidity diffusion based numerical model is proposed to simulate the floor heave processes of swelling rock tunnel when it exposed to high humidity. The phenomenon of swelling in tunneling is ...treated as a humidity–mechanical coupled process, i.e. the stress redistribution as well the water vapor diffusion around the tunnel is taken into account. This allows one to model the observed floor heaves realistically without considering the complex chemical processes induced by water–rock interaction. Furthermore, the development of heave and pressure over the course of time can be studied. The swelling rock is considered as an elasto-plastic material with damage threshold, which allows one to predict the large heaves of a tunnel floor that are often observed in-situ. The relationship between the mechanical damage and humidity diffusion are discussed at the mesoscopic level. By studying the influence of parameters in the numerical model on the floor heave behavior, the time-dependent deformation and failure processes of tunnel under high humid condition are discussed in detail. The deformations at the floor level are larger than that of sidewalls interpreted here as a consequence of different humid boundary conditions. The numerical results provide a better understanding of time-dependent behavior of floor heave of tunnel under the high humid condition.
► A humidity diffusion based model is proposed to simulate the floor heave of tunnel. ► The floor heave is greatly depending on the degradation by humidity corrosion. ► The floor heave is sensitive to the lateral pressure and the swelling coefficient. ► The time-dependent deformation is caused by stress and environmental corrosion.
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