Simulated microgravity reduces intracellular-free calcium concentration by inhibiting calcium channels in primary mouse osteoblasts.

Calcium homeostasis in osteoblasts plays fundamental roles in the physiology and pathology of bone tissue. Various types of mechanical stimuli promote osteogenesis and increase bone formation elicit increases in intracellular-free calcium concentration in osteoblasts. However, whether microgravity, a condition of mechanical unloading, exerts an influence on intracellular-free calcium concentration in osteoblasts or what mechanisms may underlie such an effect are unclear. Herein, we show that simulated microgravity reduces intracellular-free calcium concentration in primary mouse osteoblasts. In addition, simulated microgravity substantially suppresses the activities of L-type voltage-sensitive calcium channels, which selectively allow calcium to cross the plasma membrane from the extracellular space. Moreover, the functional expression of ryanodine receptors and inositol 1,4,5-trisphosphate receptors, which mediate the release of calcium from intracellular storage, decreased under simulated microgravity conditions. These results suggest that simulated microgravity substantially reduces intracellular-free calcium concentration through inhibition of calcium channels in primary mouse osteoblasts. Our study may provide a novel mechanism for microgravity-induced detrimental effects in osteoblasts, offering a new avenue to further investigate bone loss induced by mechanical unloading.

Earth's youngest banded iron formation implies ferruginous conditions in the Early Cambrian ocean.

It has been proposed that anoxic and iron-rich (ferruginous) marine conditions were common through most of Earth history. This view represents a major shift in our understanding of the evolution of marine chemistry. However, thus far, evidence for ferruginous conditions comes predominantly from Fe-speciation data. Given debate over these records, new evidence for Fe-rich marine conditions is a requisite if we are to shift our view regarding evolution of the marine redox landscape. Here we present strong evidence for ferruginous conditions by describing a suite of Fe-rich chemical sedimentary rocks-banded iron formation (BIF)--deposited during the Early Cambrian in western China. Specifically, we provide new U-Pb geochronological data that confirm a depositional age of ca. 527 Ma for this unit, as well as rare earth element (REE) data are consistent with anoxic deposition. Similar to many Algoma-type Precambrian iron formations, these Early Cambrian sediments precipitated in a back-arc rift basin setting, where hydrothermally sourced iron drove the deposition of a BIF-like protolith, the youngest ever reported of regional extent without direct links to volcanogenic massive sulphide (VMS) deposits. Their presence indicates that marine environments were still characterized by chemical- and redox-stratification, thus supporting the view that-despite a dearth of modern marine analogues-ferruginous conditions continued to locally be a feature of early Phanerozoic seawater.

miR-33-5p, a novel mechano-sensitive microRNA promotes osteoblast differentiation by targeting Hmga2.

MicroRNAs (miRNAs) interfere with the translation of specific target mRNAs and are thought to thereby regulate many cellular processes. However, the role of miRNAs in osteoblast mechanotransduction remains to be defined. In this study, we investigated the ability of a miRNA to respond to different mechanical environments and regulate mechano-induced osteoblast differentiation. First, we demonstrated that miR-33-5p expressed by osteoblasts is sensitive to multiple mechanical environments, microgravity and fluid shear stress. We then confirmed the ability of miR-33-5p to promote osteoblast differentiation. Microgravity or fluid shear stress influences osteoblast differentiation partially via miR-33-5p. Through bioinformatics analysis and a luciferase assay, we subsequently confirmed that Hmga2 is a target gene of miR-33-5p that negatively regulates osteoblast differentiation. Moreover, miR-33-5p regulates osteoblast differentiation partially via Hmga2. In summary, our findings demonstrate that miR-33-5p is a novel mechano-sensitive miRNA that can promote osteoblast differentiation and participate in the regulation of differentiation induced by changes in the mechanical environment, suggesting this miRNA as a potential target for the treatment of pathological bone loss.

miRNA-132-3p inhibits osteoblast differentiation by targeting Ep300 in simulated microgravity.

Recent studies have demonstrated that miRNAs can play important roles in osteoblast differentiation and bone formation. However, the function of miRNAs in bone loss induced by microgravity remains unclear. In this study, we investigated the differentially expressed miRNAs in both the femur tissues of hindlimb unloading rats and primary rat osteoblasts (prOB) exposed to simulated microgravity. Specifically, miR-132-3p was found up-regulated and negatively correlated with osteoblast differentiation. Overexpression of miR-132-3p significantly inhibited prOB differentiation, whereas inhibition of miR-132-3p function yielded an opposite effect. Furthermore, silencing of miR-132-3p expression effectively attenuated the negative effects of simulated microgravity on prOB differentiation. Further experiments confirmed that E1A binding protein p300 (Ep300), a type of histone acetyltransferase important for Runx2 activity and stability, was a direct target of miR-132-3p. Up-regulation of miR-132-3p by simulated microgravity could inhibit osteoblast differentiation in part by decreasing Ep300 protein expression, which, in turn, resulted in suppression of the activity and acetylation of Runx2, a key regulatory factor of osteoblast differentiation. Taken together, our findings are the first to demonstrate that miR-132-3p can inhibit osteoblast differentiation and participate in the regulation of bone loss induced by simulated microgravity, suggesting a potential target for counteracting decreases in bone formation.

MiR-103 inhibits osteoblast proliferation mainly through suppressing Cav1.2 expression in simulated microgravity.

Emerging evidence indicates that microRNAs (miRNAs) play important roles in modulating osteoblast function and bone formation. However, the influence of miRNA on osteoblast proliferation and the possible mechanisms underlying remain to be defined. In this study, we aimed to investigate whether miR-103 regulates osteoblast proliferation under simulated microgravity condition through regulating Cav1.2, the primary subunit of L-type voltage sensitive calcium channels (LTCCs). We first investigated the effect of simulated microgravity on osteoblast proliferation and the outcomes clearly demonstrated that the mechanical unloading inhibits MC3T3-E1 osteoblast-like cell proliferation. Using quantitative Real-Time PCR (qRT-PCR), we provided data showing that miR-103 was up-regulated in response to simulated microgravity. In addition, we observed that up-regulation of miR-103 inhibited and down-regulation of miR-103 promoted osteoblast proliferation under simulated microgravity condition. Furthermore, knocking-down or over-expressing miR-103, respectively, up- or down-regulated the level of Cav1.2 expression and LTCC currents, suggesting that miR-103 acts as an endogenous attenuator of Cav1.2 in osteoblasts under simulated microgravity condition. More importantly, we showed that the effect of miR-103 on osteoblast proliferation was diminished in simulated microgravity, when co-transfecting miR-103 mimic or inhibitor with Cav1.2 siRNA. Taken together, our data suggest that miR-103 inhibits osteoblast proliferation mainly through suppression of Cav1.2 expression under simulated microgravity condition. This work may provide a novel mechanism of microgravity-induced detrimental effects on osteoblast proliferation, identifying miR-103 as a novel possible therapeutic target in bone remodeling disorders in this mechanical unloading.

Simulated microgravity inhibits L-type calcium channel currents partially by the up-regulation of miR-103 in MC3T3-E1 osteoblasts.

L-type voltage-sensitive calcium channels (LTCCs), particularly Cav1.2 LTCCs, play fundamental roles in cellular responses to mechanical stimuli in osteoblasts. Numerous studies have shown that mechanical loading promotes bone formation, whereas the removal of this stimulus under microgravity conditions results in a reduction in bone mass. However, whether microgravity exerts an influence on LTCCs in osteoblasts and whether this influence is a possible mechanism underlying the observed bone loss remain unclear. In the present study, we demonstrated that simulated microgravity substantially inhibited LTCC currents and suppressed Cav1.2 at the protein level in MC3T3-E1 osteoblast-like cells. In addition, reduced Cav1.2 protein levels decreased LTCC currents in MC3T3-E1 cells. Moreover, simulated microgravity increased miR-103 expression. Cav1.2 expression and LTCC current densities both significantly increased in cells that were transfected with a miR-103 inhibitor under mechanical unloading conditions. These results suggest that simulated microgravity substantially inhibits LTCC currents in osteoblasts by suppressing Cav1.2 expression. Furthermore, the down-regulation of Cav1.2 expression and the inhibition of LTCCs caused by mechanical unloading in osteoblasts are partially due to miR-103 up-regulation. Our study provides a novel mechanism for microgravity-induced detrimental effects on osteoblasts, offering a new avenue to further investigate the bone loss induced by microgravity.

Distribution, microfabric, and geochemical characteristics of siliceous rocks in central orogenic belt, China: implications for a hydrothermal sedimentation model.

Marine siliceous rocks are widely distributed in the central orogenic belt (COB) of China and have a close connection to the geological evolution and metallogenesis. They display periodic distributions from Mesoproterozoic to Jurassic with positive peaks in the Mesoproterozoic, Cambrian--Ordovician, and Carboniferous--Permian and their deposition is enhanced by the tensional geological settings. The compressional regimes during the Jinning, Caledonian, Hercynian, Indosinian, and Yanshanian orogenies resulted in sudden descent in their distribution. The siliceous rocks of the Bafangshan-Erlihe ore deposit include authigenic quartz, syn-depositional metal sulphides, and scattered carbonate minerals. Their SiO2 content (71.08-95.30%), Ba (42.45-503.0 ppm), and ΣREE (3.28-19.75 ppm) suggest a hydrothermal sedimentation origin. As evidenced by the Al/(Al + Fe + Mn), Sc/Th, (La/Yb) N, and (La/Ce) N ratios and δCe values, the studied siliceous rocks were deposited in a marginal sea basin of a limited ocean. We suggest that the Bafangshan-Erlihe area experienced high- and low-temperature stages of hydrothermal activities. The hydrothermal sediments of the former stage include metal sulphides and silica, while the latter was mainly composed of silica. Despite the hydrothermal sedimentation of the siliceous rocks, minor terrigenous input, magmatism, and biological activity partly contributed to geochemical features deviating from the typical hydrothermal characteristics.

The distribution and composition characteristics of siliceous rocks from Qinzhou Bay-Hangzhou Bay joint belt, South China: constraint on the tectonic evolution of plates in South China.

The Qinzhou Bay-Hangzhou Bay joint belt is a significant tectonic zone between the Yangtze and Cathaysian plates, where plentiful hydrothermal siliceous rocks are generated. Here, the authors studied the distribution of the siliceous rocks in the whole tectonic zone, which indicated that the tensional setting was facilitating the development of siliceous rocks of hydrothermal genesis. According to the geochemical characteristics, the Neopalaeozoic siliceous rocks in the north segment of the Qinzhou Bay-Hangzhou Bay joint belt denoted its limited width. In comparison, the Neopalaeozoic Qinzhou Bay-Hangzhou Bay joint belt was diverse for its ocean basin in the different segments and possibly had subduction only in the south segment. The ocean basin of the north and middle segments was limited in its width without subduction and possibly existed as a rift trough that was unable to resist the terrigenous input. In the north segment of the Qinzhou Bay-Hangzhou Bay joint belt, the strata of hydrothermal siliceous rocks in Dongxiang copper-polymetallic ore deposit exhibited alternative cycles with the marine volcanic rocks, volcanic tuff, and metal sulphide. These sedimentary systems were formed in different circumstances, whose alternative cycles indicated the release of internal energy in several cycles gradually from strong to weak.

Epitaxial growth of single-domain graphene on hexagonal boron nitride.

Hexagonal boron nitride (h-BN) has recently emerged as an excellent substrate for graphene nanodevices, owing to its atomically flat surface and its potential to engineer graphene's electronic structure. Thus far, graphene/h-BN heterostructures have been obtained only through a transfer process, which introduces structural uncertainties due to the random stacking between graphene and h-BN substrate. Here we report the epitaxial growth of single-domain graphene on h-BN by a plasma-assisted deposition method. Large-area graphene single crystals were successfully grown for the first time on h-BN with a fixed stacking orientation. A two-dimensional (2D) superlattice of trigonal moiré pattern was observed on graphene by atomic force microscopy. Extra sets of Dirac points are produced as a result of the trigonal superlattice potential and the quantum Hall effect is observed with the 2D-superlattice-related feature developed in the fan diagram of longitudinal and Hall resistance, and the Dirac fermion physics near the original Dirac point is unperturbed. The macroscopic epitaxial graphene is in principle limited only by the size of the h-BN substrate and our synthesis method is potentially applicable on other flat surfaces. Our growth approach could thus open new ways of graphene band engineering through epitaxy on different substrates.

[Study on microarea characteristics of calcite in Archaean BIF from Wuyang area in south margin of North China Craton and its geological significances].

The results of Raman, SEM, CL and EDS analysis show that the quartz-type BIF (banded iron formation) in Tieshanmiao formation, from Wuyang area of south North China Craton mainly contains quartz, magnetite and a small quantity of calcite. In comparison, magnetites represent the highest automorphic degree, while calcites contribute to the lowest automorphic degree. In addition, the automorphic degree of the quartz lies between magnetite and calcite. In the results of Raman analysis, the crystallinity and order degree are quite diverse in the vertical direction of the calcite band-like, and this is different from the calcite vein precipitating from the upper hydrothermal fluid. There are obvious plastic flow happening to calcite particles. During the process of plastic flow, the calcites are finally filled in the space between quartz and magnetite. This is the reason why the cross sectional shape and distributional characteristics of calcite aggregate are controlled by the particles of quartz and magnetite, which is also evidenced by the calcite filled into the slight interspace between two particles of quartz. In the Raman analysis, there are apparent differences of microarea component in calcite band-like, and this denotes that it is produced by the plastic flow and concourse process. What's more, the calcite acts as the migration intermedium of tiny magnetite during their concourse and crystallization processes, which is witnessed by the concentrated particles of magnetite in small size in local parts of the calcites. With the help of calcite, the small magnetite particles join together to crystallize with bigger size or form aggregate of minerals.

Reducing the contact resistance of SiNW devices by employing a heavily doped carrier injection layer.

Silicon nanowires (SiNWs) are promising building blocks for future electronic devices. In SiNW-based devices, reducing the contact resistance of SiNW-metal as much as possible is critically important. Here we report a simple fabrication approach for SiNW field effect transistors (FETs) with low contact resistances by employing a heavily doped carrier injection layer wrapped around SiNWs at the contact region. Both n- and p-type SiNW-FET devices with carrier injection layers were investigated, the contact resistances were one order smaller than those without carrier injection layers and only contribute less than 14.8% for n-type devices and 11.4% for p-type devices, respectively, to the total resistance. Such low contact resistance guarantees the device characteristics mainly from the channel region of SiNW-based devices.

Multilevel resistive switching in planar graphene/SiO2 nanogap structures.

We report a planar graphene/SiO(2) nanogap structure for multilevel resistive switching. Nanosized gaps created on a SiO(2) substrate by electrical breakdown of nanographene electrodes were used as channels for resistive switching. Two-terminal devices exhibited excellent memory characteristics with good endurance up to 10(4) cycles, long retention time more than 10(5) s, and fast switching speed down to 500 ns. At least five conduction states with reliability and reproducibility were demonstrated in these memory devices. The mechanism of the resistance switching effect was attributed to a reversible thermal-assisted reduction and oxidation process that occurred at the breakdown region of the SiO(2) substrate. In addition, the uniform and wafer-size nanographene films with controlled layer thickness and electrical resistivity were grown directly on SiO(2) substrates for scalable device fabrications, making it attractive for developing high-density and low-cost nonvolatile memories.

Growth, characterization, and properties of nanographene.

A systematic study on nanographene grown directly on silicon dioxide substrates is reported. The growth is carried out in a remote plasma-enhanced chemical vapor deposition system at a low temperature of around 550 °C with methane gas as the carbon source. Atomic force microscopy is used to characterize the nanographene morphology, and Raman spectroscopy, X-ray photoelectron spectroscopy, and scanning tunneling microscopy are exploited to identify the in-plane sp(2) bonding structures of nanographene samples. Electrical transport properties are measured at various temperatures down to 4 K. Tunneling effects, minimal conductance at the charge-neutral point, sheet resistances, and Dirac point position at different channel lengths are investigated. In addition, nanographene film possesses high transmittance properties, as indicated by transmittance spectra. Nanographene devices are fabricated from rippled structures, and show great promise for strain-gauge sensor applications.

Observation of Raman g-peak split for graphene nanoribbons with hydrogen-terminated zigzag edges.

Raman scattering of individual hydrogen-terminated zigzag-edged graphene nanoribbons (Z-GNRs) was studied with focus on the G-peak. In addition to the bulk graphene G-peak appearing at ∼1594 cm(-1) (G(+)), an edge-related G-peak at ∼1583 cm(-1) (G(-)) was observed for Z-GNRs. This additional Raman vibrational mode originates from the zigzag edges where localized metallic edge states are present. The relative intensity ratio G(-)/G(+) displays a strong dependence on the ribbon width (W). It increases gradually with decreasing W, and the G(+) finally vanishes at W = 5(±3) nm. Polarized Raman scattering was also employed to confirm the four-fold symmetry of the split TO modes, and the results are in good agreement with previous theoretical predictions. Our work offers the first direct experimental evidence to confirm the validity of predicted Raman scattering of GNRs.

Super-elastic graphene ripples for flexible strain sensors.

In this study, we report a buckling approach for graphene and graphene ribbons on stretchable elastomeric substrates. Stretched polydimethylsiloxane (PDMS) films with different prestrains were used to receive the transferred graphene, and nanoscale periodical buckling of graphene was spontaneously formed after strain release. The morphology and periodicity of the as-formed graphene ripples are dependent strongly on their original shapes and substrates' prestrains. Regular periodicity of the ripples preferred to form for narrow graphene ribbons, and both the amplitude and periodicity are reduced with the increase of prestrain on PDMS. The graphene ripples have the ability to afford large strain deformation, thus making it ideal for flexible electronic applications. It was demonstrated that both graphene ribbon and nanographene film ripples could be used for strain sensors, and their resistance changes upon different strains were studied. This simple and controllable process of buckled graphene provides a feasible fabrication for graphene flexible electronic devices and strain sensors due to its novel mechanical and electrical properties.