[Regulatory relationship between lncRNA KCNQ1OT1 and miR-146a-3p in preeclampsia].

Objective: To observe the changes of the expression level of long non-coding RNA (lncRNA) KCNQ1OT1 and microRNA (miR)-146a-3p in placenta tissues of preeclampsia (PE) patients, as well as their effect and mechanism on the biological functions of trophoblast cells. Methods: A total of 45 cases of hospitalized PE patients in Hainan General Hospital from July 2017 to July 2018 were selected as the PE group, 55 normal pregnant women during the same period were chosed as the control group. The expression level of KCNQ1OT1 mRNA and miR-146a-3p in the placenta tissues between two groups were detected by using quantitative real time (qRT)-PCR. Pearson's test was furtherly analyzed the correlation between them. Human trophoblast cell line (HTR8/SVneo) were randomly divided into control and lipopolysaccharide (LPS) groups, and then LPS group were divide into four sub-groups,included LPS group, short hairpin RNA (sh)-KCNQ1OT1 (after silencing the expression of KCNQ1OT1), miR-146a-3p inhibitor and sh-KCNQ1OT1+miR-146a-3p inhibitor. The targeting relationship between KCNQ1OT1 and miR-146a-3p were predicted by bioinformatics software and confirmed by luciferase assay. The cell proliferation and invasion capacities were respectively detected by cell counting kit-8 (CCK-8) and transwell assay. The expression level of KCNQ1OT1 mRNA and miR-146a-3p were detected by qRT-PCR and the protein expression level of CXC chemokine ligand 12 （CXCL12） and CXC chemokine receptor type 4 (CXCR4) were tested by western blot. Results: (1) The mRNA expression level of KCNQ1OT1 in the placenta of PE group was lower than that of control group (0.23±0.03 vs 0.51±0.04, P<0.05), and the miR-146a-3p expression level was higher than that of the control group (0.49±0.03 vs 0.31±0.03, P<0.05), there were statistical significant differences between the two groups. (2) Luciferase assay showed that there was a targeting relationship between KCNQ1OT1 and mir-146a-3p. Compared with the control group, the mRNA expression level of KCNQ1OT1 in the LPS group were significantly decreased (0.91±0.03 vs 0.35±0.03, P<0.05), and the expression level of miR-146a-3p were significantly increased (0.22±0.03 vs 0.63±0.04, P<0.05). The cell proliferation, invasion and migration capacities and the protein expression of CXCL12 and CXCR4 significantly reduced in the LPS group compared with control group (all P<0.05). The mRNA expression level of KCNQ1OT1 (0.23±0.03) in the sh-KCNQ1OT1 group were further decreased, the expression of miR-146a-3p (0.85±0.03) were further increased, and the cell proliferation, invasion and migration capacities and the protein expression of CXCL12 and CXCR4 were all further reduced compared with control group，there were significant difference between two groups (all P<0.05). Comparing the miR-146a-3p inhibitor group, and sh-KCNQ1OT1+miR-146a-3p inhibitor group with the sh-KCNQ1OT1 group, respectively, the expression level of KCNQ1OT1 mRNA (0.78±0.04 vs 0.50±0.03) increased, and the expression level of miR-146a-3p (0.42±0.03 vs 0.46±0.03) decreased, the cell proliferation, invasion and migration capacities and the protein expression of CXCL12 and CXCR4 were all increased ,there were statistically significant differences (all P<0.05). Conclusion: KCNQ1OT1 could target the regulation of miR-146a-3p through CXCL12/CXCR4 pathway in the proliferation, invasion an migration of HTR8/SVneo cells, which may be involved in the pathogenesis of PE.

Dual heterogeneous structures lead to ultrahigh strength and uniform ductility in a Co-Cr-Ni medium-entropy alloy.

Alloys with ultra-high strength and sufficient ductility are highly desired for modern engineering applications but difficult to develop. Here we report that, by a careful controlling alloy composition, thermomechanical process, and microstructural feature, a Co-Cr-Ni-based medium-entropy alloy (MEA) with a dual heterogeneous structure of both matrix and precipitates can be designed to provide an ultra-high tensile strength of 2.2 GPa and uniform elongation of 13% at ambient temperature, properties that are much improved over their counterparts without the heterogeneous structure. Electron microscopy characterizations reveal that the dual heterogeneous structures are composed of a heterogeneous matrix with both coarse grains (10∼30 µm) and ultra-fine grains (0.5∼2 µm), together with heterogeneous L12-structured nanoprecipitates ranging from several to hundreds of nanometers. The heterogeneous L12 nanoprecipitates are fully coherent with the matrix, minimizing the elastic misfit strain of interfaces, relieving the stress concentration during deformation, and playing an active role in enhanced ductility.

Atomic Configuration of Point Defect Clusters in Ion-Irradiated Silicon Carbide.

Silicon Carbide (SiC) is a promising cladding material for accident-tolerant fuel in light water reactors due to its excellent resistance to chemical attacks at high temperatures, which can prevent severe accident-induced environmental disasters. Although it has been known for decades that radiation-induced swelling at low temperatures is driven by the formation of black spot defects with sizes smaller than 2 nm in irradiated SiC, the structure of these defect clusters and the mechanism of lattice expansion have not been clarified and remain as one of the most important scientific issues in nuclear materials research. Here we report the atomic configuration of defect clusters using Cs-corrected transmission electron microscopy and molecular dynamics to determine the mechanism of these defects to radiation swelling. This study also provides compelling evidence that irradiation-induced point defect clusters are vacancy-rich clusters and lattice expansion results from the homogenous distribution of unrecovered interstitials in the material.

Prospects for atomic resolution in-line holography for a 3D determination of atomic structures from single projections.

It is now established that the 3D structure of homogeneous nanocrystals can be recovered from in-line hologram of single projections. The method builds on a quantitative contrast interpretation of electron exit wave functions. Since simulated exit wave functions of single and bilayers of graphene reveal the atomic structure of carbon-based materials with sufficient resolution, we explore theoretically how the approach can be expanded beyond periodic carbon-based materials to include non-periodic molecular structures. We show here theoretically that the 3D atomic structure of randomly oriented oleic acid molecules can be recovered from a single projection.

Structure-based modelling, scoring, screening, and in vitro kinase assay of anesthetic pkc inhibitors against a natural medicine library.

Protein kinase C (PKC) is an intracellular effector of the inositol phosphate-mediated signal transduction pathway. Evidence is emerging that certain general anaesthetics can influence the activity of PKC by interacting with the regulatory domain of the enzyme, and targeting PKC kinase domain is considered as a strategy to modulate the anaesthetic effects. Here, an integrated method was used to perform virtual screening against a large library of natural compounds for the discovery of new and potent PKC modulators. A number of hits were identified and their inhibitory activity against PKC kinase domain was measured by using a standard kinase assay protocol. Three and five compounds were determined to have high and moderate activities with IC50 values at nanomolar and micromolar levels, respectively. These compounds can be considered as promising lead molecular entities to develop efficacious anaesthetic modulators. Structural examination revealed a variety of nonbonded interactions such as hydrogen bonds, cation-π contacts, and hydrophobic forces across the complex interface of PKC with the identified compounds. This study helps to establish an integrative approach to rational kinase inhibitor discovery by efficiently exploiting various existing natural products.

Extracting nano-gold from HAuCl4 solution manipulated with electrons.

It has been fundamentally important and technologically challenging to elucidate the migration behavior of solute atoms in solvents, which can help to understand the growth of nanoparticles. Recently, ascribed to the booming development of start-of-the-art liquid environmental transmission electron microscopes (LETEMs), it has become possible to disclose, in situ, the phase segregation mechanism of elementary units in a solvent at the nanoscale. In addition, bombardment with an electron beam can induce a locally positive potential, with the application of low-conductive Si3N4 and water in LETEMs. Such merits can enable modification of the dynamic distribution and reductive behavior of the solute ions in water solutions. Herein we report the migration and segregation behaviors of Au atoms in a solvent during real time, by exploiting a charging effect in a dilute HAuCl4 water solution under electron irradiation. As a consequence, the growth kinetics of Au nanoparticles can be successfully controlled with an accelerated kinetics model. Through dynamically capturing the segregation behavior of the hydrated atoms, a resultant size-controlling mechanism is clarified with three cycles of nanoparticle growth behavior. A new insight is consequently gained into microscopically manipulating the hydrothermal synthesis of nanomaterials.

In-line three-dimensional holography of nanocrystalline objects at atomic resolution.

Resolution and sensitivity of the latest generation aberration-corrected transmission electron microscopes allow the vast majority of single atoms to be imaged with sub-Ångstrom resolution and their locations determined in an image plane with a precision that exceeds the 1.9-pm wavelength of 300 kV electrons. Such unprecedented performance allows expansion of electron microscopic investigations with atomic resolution into the third dimension. Here we report a general tomographic method to recover the three-dimensional shape of a crystalline particle from high-resolution images of a single projection without the need for sample rotation. The method is compatible with low dose rate electron microscopy, which improves on signal quality, while minimizing electron beam-induced structure modifications even for small particles or surfaces. We apply it to germanium, gold and magnesium oxide particles, and achieve a depth resolution of 1-2 Å, which is smaller than inter-atomic distances.

Autoimmune risk loci of IL12RB2, IKZF1, XKR6, TMEM39A and CSK in Chinese patients with systemic lupus erythematosus.

Recent genome-wide or follow-up studies conducted in European or Caucasian populations have identified single nucleotide polymorphisms (SNPs) conferring increased risk to autoimmune diseases. It is unclear whether these observations can apply to systemic lupus erythematosus (SLE) in China. An association study was performed on 395 SLE patients and 378 healthy controls recruited from the Chinese population, in which the IL12RB2 rs3790567, IKZF1 rs2366293, XKR6 rs4240671, TMEM39A rs1132200 and CSK rs34933034 polymorphisms were examined by Matrix Assisted Laser Desorption Time of Flight Mass Spectrometry. The frequency of the A allele of IL12RB2 rs3790567 was lower in the cases compared with the controls (24.8% vs 30.2%, P = 0.018) and significant difference among the AA, AG and GG genotypes of rs3790567 was detected between the SLE patients and healthy controls (P = 0.020). We also found a statistically significant difference in the dominant model (GG+AG vs AA, P = 0.008). There was no correlation between the genotypes and specific sub-phenotypes in the current cohort. Associations with IKZF1 rs2366293, XKR6 rs4240671, TMEM39A rs1132200 and CSK rs34933034 were also lacking (P > 0.05). The results supported the theory that IL12RB2 is associated with SLE in the Chinese population.

Association of PELI1 polymorphisms in systemic lupus erythematosus susceptibility in a Chinese population.

OBJECTIVE: Studies in animal models have indicated that Pellino 1 is involved in inflammatory and autoimmune diseases, such as systemic lupus erythematosus (SLE). The current study was designed to determine whether PELI1 confers genetic susceptibility to SLE in humans, as assessed in a Chinese Han population. METHODS: Blood samples were drawn from patients diagnosed with SLE and healthy volunteers. Three single nucleotide polymorphism (SNP) loci with a minor allele frequency of at least 0.05 were chosen to evaluate the correlation between PELI1 genotype and the incidence of SLE. RESULTS: There was a significant difference in the frequency distribution of the rs329497 allele between the SLE patients and the healthy controls (A vs. G; Bonferroni corrected p = 0.036, odds ratio = 0.75, 95% confidence interval = 0.60-0.94). No differences in the genotype and allele frequencies of other SNP loci were observed between the two groups. Furthermore, the alleles and genotypes of the three SNPs were not associated with lupus nephritis. CONCLUSION: In the Chinese Han population, PELI1 SNPs may be associated with SLE susceptibility.

3D reconstruction of nanocrystalline particles from a single projection.

This paper describes an approach to retrieve the three-dimensional atomic structure of a nanocrystalline particle from the reconstructed electron exit wave function in a single projection direction. The method employs wave propagation to determine the local exit surface of each atomic column together with its mass. The exit wave in between colums is used as internal calibration so as to remove the background noise and improve the precision to the level of single atom sensitivity. The validity of the approach is tested with exit wave functions of a gold wedge reconstructed from simulated images containing different levels of noise.

Imaging cells and sub-cellular structures with ultrahigh resolution full-field X-ray microscopy.

Our experimental results demonstrate that full-field hard-X-ray microscopy is finally able to investigate the internal structure of cells in tissues. This result was made possible by three main factors: the use of a coherent (synchrotron) source of X-rays, the exploitation of contrast mechanisms based on the real part of the refractive index and the magnification provided by high-resolution Fresnel zone-plate objectives. We specifically obtained high-quality microradiographs of human and mouse cells with 29 nm Rayleigh spatial resolution and verified that tomographic reconstruction could be implemented with a final resolution level suitable for subcellular features. We also demonstrated that a phase retrieval method based on a wave propagation algorithm could yield good subcellular images starting from a series of defocused microradiographs. The concluding discussion compares cellular and subcellular hard-X-ray microradiology with other techniques and evaluates its potential impact on biomedical research.

A method to determine the local surface profile from reconstructed exit waves.

Reconstructed exit waves are useful to quantify unknown structure parameters such as the position and composition of the atom columns at atomic scale. Existing techniques provide a complex wave in a flat plane which is close to the plane where the electrons leave the atom columns. However, due to local deviation in the flatness of the exit surface, there will be an offset between the plane of reconstruction and the actual exit of a specific atom column. Using the channelling theory, it has been shown that this defocus offset can in principle be determined atom column-by-atom column. As such, the surface roughness could be quantified at atomic scale. However, the outcome strongly depends on the initial plane of reconstruction especially in a crystalline structure. If this plane is further away from the true exit, the waves of the atom columns become delocalized and interfere mutually which strongly complicates the interpretation of the exit wave in terms of the local structure. In this paper, we will study the delocalization with defocus using the channelling theory in a more systematic way.

Nanocontact resistance and structural disorder induced resistivity variation in metallic metal-oxide nanowires.

Several systems of metallic metal-oxide nanowires (NWs), including pure RuO2 and as-implanted and annealed Ru(0.98)Cu(0.02)O2 and Ru(0.93)Cu(0.07)O2 NWs, have been employed in two-probe electrical characterizations by using a transmission electron microscope-scanning tunneling microscope technique with a gold tip. Thermal, mechanical, and electron beam exposing treatments are consecutively applied to reduce the electrical contact resistance, generated from the interface between the NW and the gold tip, so as to evaluate the intrinsic NW resistance. It is found that the residual contact resistance cannot be entirely removed. For each system of metallic metal-oxide NWs, several tens of NWs are applied to electrical characterizations and the total resistances unveil a linear dependence on the ratio of the length to the area of the NWs. As a result, the average resistivity and the contact resistance of the metallic metal-oxide NWs could be evaluated at room temperatures. The average resistivities of pure RuO2 NWs agree well with the results obtained from standard two- and four-probe electrical-transport measurements. In addition, the as-implanted Cu-RuO2 NWs reveal disordered crystalline structures in high-resolution TEM images and give higher resistivities in comparison with that of pure RuO2 NWs. The residual contact resistances of all kinds of metallic metal-oxide NWs unveil, more surprisingly, an approximation value of several kilohms, even though the average resistivities of these NWs change by more than one order of magnitude. It is argued that the ductile gold tip makes one or more soft contacts on the stiff metal-oxide NWs with nanometer roughness and the nanocontacts on the NWs contribute to the electrical contact resistance.

Quantitative analysis of defects and domain boundaries in mesoporous SBA-16 films.

Some quantitative structural analyses on defects and domain boundaries observed in SBA-16 films were performed using the lattice concept and geometric phase method. These analyses show that there exist low angle, high angle and translational anti-phase domain boundaries in SBA-16 films. While some of the domain boundaries bear analogue to those found in normal solid crystals, others are similar to that found in the liquid crystals. In particular near Sigma11 and Sigma13b high angle boundaries were observed. On the one hand the Sigma11 boundaries were found to exist with or without steps (ledge) associated with them depending on whether or not the boundary plane is parallel to the densely packed lattice plane. On the other hand segments of the boundary plane in the Sigma13b boundary were found being always associated with densely packed lattice plane, with the {011} type of lattice plane in one domain being parallel to the {112} type of plane in the other domain. The translational domain boundary was observed to have a translation vector having a projected component of (1/2) <110> on the (111) plane. The bending deformation similar to that found in the nematics liquid crystal was also observed and quantitatively analyzed using the geometric phase method, and rotational field associated with the deformation was identified.

The wrap-around problem and optimal padding in the exit wave reconstruction using HRTEM images.

A free fast Fourier transform software FFTW (www.fftw.org) is used in the exit wave reconstruction and shown to be able to handle images of any size effectively. The wrap-around problem commonly encountered in the exit wave reconstruction is investigated, and a new padding scheme is proposed and its performance is investigated. It is shown that while the usual wrap-around problem may be solved via padding the input high-resolution transmission electron microscopy (HRTEM) images with zero or averaged image intensities, the reconstructed exit wave at its boundary is inevitably distorted by the discontinuity of image intensities at the boundary. The proposed new padding scheme is shown to be able to provide a good estimate of the image intensities immediately outside the boundaries of the HRTEM images, reducing the estimated image intensity discontinuity across the boundaries and therefore providing a larger undistorted view of the exit wave.

Spatial incoherence in phase retrieval based on focus variation.

We investigate the effect of spatial incoherence on two methods of phase retrieval based on focus variation: the transport of intensity equation and iterative wave function reconstruction. Spatial incoherence provides an upper bound on the defocus step size which should be used in each case. The requirement that phase information manifests itself in sufficient variation in the defocused images provides a lower bound on the defocus step size which should be used in each case. The scaling of these upper and lower bounds with object size and imaging resolution differs in such a way that, given the spatial incoherence properties of the source, for sufficiently low resolutions neither technique can retrieve phase information. The regions of applicability of the two techniques are discussed.

Orbital susceptibilities of PbSe quantum dots.

Different sizes of three-dimensional PbSe quantum dots have been synthesized for the study of orbital magnetic susceptibilities. Two types of orbital susceptibilities have been found, including the Curie susceptibility and finite-size corrections to the Landau susceptibility. The Curie term of a quantum dot manifests itself in the temperature dependence of magnetic susceptibility at low temperatures, while the field dependence of differential susceptibility at high temperatures shows finite-size corrections to the Landau susceptibility. Both of the two kinds of orbital susceptibility, estimated per quantum dot, show linear dependence on the size.

Red tides in the Gulf of Mexico: Where, when, and why?

[1] Independent data from the Gulf of Mexico are used to develop and test the hypothesis that the same sequence of physical and ecological events each year allows the toxic dinoflagellate Karenia brevis to become dominant. A phosphorus-rich nutrient supply initiates phytoplankton succession, once deposition events of Saharan iron-rich dust allow Trichodesmium blooms to utilize ubiquitous dissolved nitrogen gas within otherwise nitrogen-poor sea water. They and the co-occurring K. brevis are positioned within the bottom Ekman layers, as a consequence of their similar diel vertical migration patterns on the middle shelf. Upon onshore upwelling of these near-bottom seed populations to CDOM-rich surface waters of coastal regions, light-inhibition of the small red tide of ~1 ug chl l(-1) of ichthytoxic K. brevis is alleviated. Thence, dead fish serve as a supplementary nutrient source, yielding large, self-shaded red tides of ~10 ug chl l(-1). The source of phosphorus is mainly of fossil origin off west Florida, where past nutrient additions from the eutrophied Lake Okeechobee had minimal impact. In contrast, the P-sources are of mainly anthropogenic origin off Texas, since both the nutrient loadings of Mississippi River and the spatial extent of the downstream red tides have increased over the last 100 years. During the past century and particularly within the last decade, previously cryptic Karenia spp. have caused toxic red tides in similar coastal habitats of other western boundary currents off Japan, China, New Zealand, Australia, and South Africa, downstream of the Gobi, Simpson, Great Western, and Kalahari Deserts, in a global response to both desertification and eutrophication.