MicroRNA-214-3p Ameliorates LPS-Induced Cardiomyocyte Injury by Inhibiting Cathepsin B.

Myocardial injury is a common complication of sepsis. MicroRNA (miRNA) miR-214-3p is protective against myocardial injury caused by sepsis, but its mechanism in lipopolysaccharide (LPS)- induced cardiomyocyte injury is still unclear. An AC16 cell injury model was induced by LPS treatment. Cell Counting Kit-8 and flow cytometry assay showed decreased cell viability and increased apoptosis in LPS-treated AC16 cells. The levels of caspase- 3, Bax, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), myosin 6 (Myh6), myosin 7 (Myh7), reactive oxygen species (ROS), and malondialdehyde (MDA) were increased in LPS-treated AC16 cells, but the levels of Bcl-2 and superoxide dismutase (SOD) were decreased. MiR-214-3p was down-regulated and cathepsin B (CTSB) was upregulated in LPS-treated AC16 cells. At the same time, miR-214-3p could target CTSB and reduce its expression. We also found that a miR-214-3p mimic or CTSB silencing could significantly reduce LPSinduced apoptosis, decrease ROS, MDA, caspase-3, and Bax and increase SOD and Bcl-2. CTSB silencing could significantly reduce ANP, BNP, Myh6, and Myh7 in LPS-treated AC16 cells. The effects of CTSB silencing were reversed by a miR-214-3p inhibitor. In summary, miR-214-3p could inhibit LPSinduced myocardial injury by targeting CTSB, which provides a new idea for myocardial damage caused by sepsis.

Exponentially selective molecular sieving through angstrom pores.

Two-dimensional crystals with angstrom-scale pores are widely considered as candidates for a next generation of molecular separation technologies aiming to provide extreme, exponentially large selectivity combined with high flow rates. No such pores have been demonstrated experimentally. Here we study gas transport through individual graphene pores created by low intensity exposure to low kV electrons. Helium and hydrogen permeate easily through these pores whereas larger species such as xenon and methane are practically blocked. Permeating gases experience activation barriers that increase quadratically with molecules' kinetic diameter, and the effective diameter of the created pores is estimated as ∼2 angstroms, about one missing carbon ring. Our work reveals stringent conditions for achieving the long sought-after exponential selectivity using porous two-dimensional membranes and suggests limits on their possible performance.

Publisher Correction: Control of electron-electron interaction in graphene by proximity screening.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Control of electron-electron interaction in graphene by proximity screenings.

Electron-electron interactions play a critical role in many condensed matter phenomena, and it is tempting to find a way to control them by changing the interactions' strength. One possible approach is to place a studied system in proximity of a metal, which induces additional screening and hence suppresses electron interactions. Here, using devices with atomically-thin gate dielectrics and atomically-flat metallic gates, we measure the electron-electron scattering length in graphene and report qualitative deviations from the standard behavior. The changes induced by screening become important only at gate dielectric thicknesses of a few nm, much smaller than a typical separation between electrons. Our theoretical analysis agrees well with the scattering rates extracted from measurements of electron viscosity in monolayer graphene and of umklapp electron-electron scattering in graphene superlattices. The results provide a guidance for future attempts to achieve proximity screening of many-body phenomena in two-dimensional systems.

Limits on gas impermeability of graphene.

Despite being only one-atom thick, defect-free graphene is considered to be completely impermeable to all gases and liquids1-10. This conclusion is based on theory3-8 and supported by experiments1,9,10 that could not detect gas permeation through micrometre-size membranes within a detection limit of 105 to 106 atoms per second. Here, using small monocrystalline containers tightly sealed with graphene, we show that defect-free graphene is impermeable with an accuracy of eight to nine orders of magnitude higher than in the previous experiments. We are capable of discerning (but did not observe) permeation of just a few helium atoms per hour, and this detection limit is also valid for all other gases tested (neon, nitrogen, oxygen, argon, krypton and xenon), except for hydrogen. Hydrogen shows noticeable permeation, even though its molecule is larger than helium and should experience a higher energy barrier. This puzzling observation is attributed to a two-stage process that involves dissociation of molecular hydrogen at catalytically active graphene ripples, followed by adsorbed atoms flipping to the other side of the graphene sheet with a relatively low activation energy of about 1.0 electronvolt, a value close to that previously reported for proton transport11,12. Our work provides a key reference for the impermeability of two-dimensional materials and is important from a fundamental perspective and for their potential applications.

LncRNA H19 promotes glioma angiogenesis through miR-138/HIF-1α/VEGF axis.

Glioma is one of the most common and aggressive malignant primary brain tumors with high recurrence rate and mortality rate and heavily depends on the angiogenesis. LncRNA H19 has many diverse biological functions, including the regulation of cell proliferation, differentiation and metabolism. Here, we aimed to investigate the molecular mechanism of lncRNA H19 affecting angiogenesis in glioma, which could help to uncover potential target for glioma therapy. RT-qPCR analysis was performed to detect the expression of lncRNA H19 and miR-138 in HEB, U87, A172 and U373 cell lines. MTT assay was used to evaluate the cell viability. To evaluate the migration and invasion after lncRNA H19 knockdown, Transwell and wound healing assay were employed. After lncRNA H19 knockdown, protein expression of HIF 1α and VEGF was detected by western blot and tube formation was assessed. For the prediction and validation of the interaction between lncRNA H19 and miR-138, bioinformatics and luciferase assay were performed. We investigated the regulatory roles and downstream molecular mechanisms of lncRNA H19 in glioma by knockdown H19, which inhibited the proliferation, migration and angiogenesis of glioma cells. Moreover, miR-138 acted as a target of H19 as detected by luciferase reporter assays. Meanwhile, HIF-1α was also a target of miR-138 and miR-138 could also regulate the proliferation, migration and angiogenesis of glioma cells by targeting HIF-1α and affecting the expression of VEGF in turn. Our findings identified an upregulated lncRNA H19 in glioma cells, which could promote proliferation, migration, invasion and angiogenesis via miR-138/HIF-1α axis as a ceRNA. This study provided a new opportunity to advance our understanding in the potential mechanism of lncRNA in glioma angiogenesis.

Giant oscillations in a triangular network of one-dimensional states in marginally twisted graphene.

At very small twist angles of ∼0.1°, bilayer graphene exhibits a strain-accompanied lattice reconstruction that results in submicron-size triangular domains with the standard, Bernal stacking. If the interlayer bias is applied to open an energy gap inside the domain regions making them insulating, such marginally twisted bilayer graphene is expected to remain conductive due to a triangular network of chiral one-dimensional states hosted by domain boundaries. Here we study electron transport through this helical network and report giant Aharonov-Bohm oscillations that reach in amplitude up to 50% of resistivity and persist to temperatures above 100 K. At liquid helium temperatures, the network exhibits another kind of oscillations that appear as a function of carrier density and are accompanied by a sign-changing Hall effect. The latter are attributed to consecutive population of the narrow minibands formed by the network of one-dimensional states inside the gap.

Simultaneous Biofortification of Wheat with Zinc, Iodine, Selenium, and Iron through Foliar Treatment of a Micronutrient Cocktail in Six Countries.

Field experiments were conducted on wheat to study the effects of foliar-applied iodine(I) alone, Zn (zinc) alone, and a micronutrient cocktail solution containing I, Zn, Se (selenium), and Fe (iron) on grain yield and grain concentrations of micronutrients. Plants were grown over 2 years in China, India, Mexico, Pakistan, South Africa, and Turkey. Grain-Zn was increased from 28.6 mg kg-1 to 46.0 mg-1 kg with Zn-spray and 47.1 mg-1 kg with micronutrient cocktail spray. Foliar-applied I and micronutrient cocktail increased grain I from 24 µg kg-1 to 361 µg kg-1 and 249 µg kg-1, respectively. Micronutrient cocktail also increased grain-Se from 90 µg kg-1 to 338 µg kg-1 in all countries. Average increase in grain-Fe by micronutrient cocktail solution was about 12%. The results obtained demonstrated that foliar application of a cocktail micronutrient solution represents an effective strategy to biofortify wheat simultaneously with Zn, I, Se and partly with Fe without yield trade-off in wheat.

Strain-induced rich magnetic phase transitions and enhancement of magnetic stability for O-terminated h-BN nanoribbons.

Mono-layered h-BN and its derivatives are very important low-dimensional materials, which have been widely investigated so far. Here, we theoretically study the structural stability and magneto-electronic properties of oxygen (O) terminated zigzag-edged h-BN nanoribbons, especially focusing on strain tuning effects. The O dimerization at the B edge of the ribbon enhances the system stability greatly. A Poisson ratio of 0.2 and bearing a strain more than 20% can be reached. In the absence of strain, the O-terminated ribbon is a magnetic metal. However, the rich magnetic phase transitions among the non-magnetic metal, a spin gapless semiconductor, and a wide-gap half-metal can be realized continuously by applying strain in the ferromagnetic state. Thus, based on such a material feature, we can design a magnetic switch device which can work between the magnetic and non-magnetic states by strain modification. Also shown is that the magnetism stability can be enhanced to the level at room temperature upon strain, and the massless Dirac-fermion behavior for the ß-spin state can be clearly detected in the spin gapless semiconductor phase under appropriate strains.

Spin-dependent carrier mobility and its gate-voltage modifying effects for functionalized single walled black phosphorus tubes.

Phosphorene and its derivatives so far have attracted substantial research interest due to its promising properties for developing nanoscale electronic devices. Here, we present a theoretical investigation on the functionalized features, such as the improved electronic structure and carrier mobility, for armchair-edged single walled black phosphorus nanotubes (PNTs) with the substitutional doping of low-concentration transition-metal atoms (Ti, Mn, Fe, and Ni). They are predicted to be exceptional magnetic semiconductors (MSCs), such as half-semiconductor or bipolar MSC. Their spin-resolved carrier mobility at room temperature holds doping element- dependence as well as carrier and spin polarity. Particularly, the difference by two orders of magnitude for carrier mobility emerges due to different TM doping. More interestingly, the carrier mobility in armchair PNTs serving as the channel material of a spin field effect transistor is predicted to be modified strongly by a gate voltage. The enhanced carrier mobility and its gate voltage direction-dependent behavior, as well as the more obvious carrier and spin polarity of mobility, can be observed clearly under gate voltage, which further facilitates the separation of different carriers and spin states and also suggests that realistic carrier mobility is gate voltage-dependent in a field effect transistor.

NLRP12 promotes host resistance against Pseudomonas aeruginosa keratitis inflammatory responses through the negative regulation of NF-κB signaling.

OBJECTIVE: To investigate the role of NLRP12 in regulating Pseudomonas aeruginosa (P. aeruginosa) keratitis. MATERIALS AND METHODS: Real-Time-PCR and Western blot were performed to measure the NLRP12 level in corneas and bone marrow-derived macrophages (BMDMs) of C57BL/6 (B6) mice. B6 mice received a subconjunctival injection of lentivirus expressing active NLRP12 (NLRP12-lentivirus) or Ctl-lentivirus (as control), followed by infection of P. aeruginosa. The clinical score, slit lamp and bacterial plate count of mice were evaluated. In addition, myeloperoxidase (MPO) was detected to assess the infiltration of polymorphonuclear neutrophil (PMN). Cytokine levels were measured by Real Time-PCR and ELISA. Meanwhile, the bacterial burden was also evaluated. The activation of NF-κB signaling was determined by pIκBα/IκBα levels based on Western blot and NF-κB-dependent Luciferase activity on the basis of Luciferase assays using 293T cells. RESULTS: NLRP12 mRNA and protein levels were decreased in B6 corneas and BMDMs after P. aeruginosa infection. The over-expression of NLRP12 in B6 corneas significantly ameliorated the severity of corneal disease, bacterial burden, PMN infiltration and pro-inflammatory cytokine expression. In vitro analysis demonstrated that the up-regulation of NLRP12 suppressed pro-inflammatory cytokine production and enhanced bacterial clearance in RAW264.7 cells. The protein levels of pIκBα and IκBα were significantly decreased after NLRP12-lentivirus treatment compared with that of Ctl-lentivirus. NF-κB-dependent Luciferase activity was potently inhibited by NLRP12 infected with P. aeruginosa or cotransfected with the downstream signaling molecules including IKKα and IKKß in 293T cells. CONCLUSIONS: NLRP12 decreases the severity of P. aeruginosa keratitis, reduces corneal inflammation and bacterial burden through the down-regulation of the NF-κB signaling pathway.

MiRNA regulates OCT4 expression in breast cancer cells.

OBJECTIVE: Breast cancer cell infiltration, migration, and proliferation significantly affect its curative effect. Stemness gene octamer-binding transcription factor 4 (OCT4) upregulated in breast cancer tissue compared with normal control. MiRNA exhibits regulatory role in gene expression. This study adopted bioinformatics to predict the miRNA to regulate OCT4 gene and investigated its impact on breast cancer cell infiltration, migration, and proliferation. MATERIALS AND METHODS: MirBase database was analyzed to explore the potential miRNA in regulating OCT4 based on human OCT4 gene sequence. MiRNA mimics and inhibitor were synthetized and transfected to BS524 cells. qRT-PCR was applied to test miRNA and OCT4 mRNA expressions in cells at 12 h, 24 h, and 48 h after transfection. Western blot was selected to detect OCT4 protein expression. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was selected to determine cell proliferation. Scratch assay was adopted to evaluate cell migration. Transwell assay was used to analyze cell infiltration. RESULTS: MiR-145 may regulate OCT4 gene with score 82. OCT4 mRNA and protein increased at 12 h after transfection (p > 0.05). OCR4 gene significantly upregulated, cell proliferation, migration, and infiltration enhanced by miR-145 transfection compared with control (p < 0.05). OCT4 gene downregulated, while cell proliferation, infiltration, and migration markedly weakened in miR-145 inhibitor group compared with control (p < 0.05). CONCLUSIONS: MiR-145 affects breast cancer BS524 cell proliferation, infiltration, and migration via positively regulating OCT4 gene expression.

[Gene Analysis for the Sudden Death of Hypertrophic Cardiomyopathy by Whole Exome Sequencing.]

OBJECTIVES: To analyze the related pathogenicity gene mutations in a sudden death of hypertrophic cardiomyopathy （HCM） on whole exome level. METHODS: Whole exome sequencing （WES） was been performed on a sudden death case sample with pathological features of HCM by Illumina® Hiseq 2500 platform. Using hg19 as the reference sequences, the sequencing data were analyzed. Suspicious single nucleotide variants （SNV） were screened, and the conservatism and function were analyzed by the software such as PhyloP, PolyPhen-2, SIFT, etc. RESULTS: After screening, a heterozygous mutation C719R was finally identified in the gene MYBPC3 of this case. CONCLUSIONS: The molecular anatomy on whole exome level by second generation sequencing technology can help to define the molecular mechanism of HCM and provide a new mothed and thought for analysis of death cause.

High-field magnetic resonance imaging of structural alterations in first-episode, drug-naive patients with major depressive disorder.

Previous structural imaging studies have found evidence of brain morphometric changes in patients with major depressive disorder (MDD), but these studies rarely excluded compounding effects of certain important factors, such as medications and long duration of illnesses. Furthermore, the neurobiological mechanism of the macroscopic findings of structural alterations in MDD patients remains unclear. In this study, we utilized magnetization transfer imaging, a quantitative measure of the macromolecular structural integrity of brain tissue, to identify biophysical alterations, which are represented by a magnetization transfer ratio (MTR), in MDD patients. To ascertain whether MTR changes occur independent of volume loss, we also conduct voxel-based morphometry (VBM) analysis. The participants included 27 first-episode, drug-naive MDD patients and 28 healthy controls matched for age and gender. Whole-brain voxel-based analysis was used to compare MTR and gray matter volume across groups and to analyse correlations between MTR and age, symptom severity, and illness duration. The patients exhibited significantly lower MTR in the left superior parietal lobule and left middle occipital gyrus compared with healthy controls, which may be related to the attentional and cognitive dysfunction in MDD patients. The VBM analysis revealed significantly increased gray matter volume in right postcentral gyrus in MDD patients. These findings in first-episode, drug-naive MDD patients may reflect microstructural gray matter changes in the parietal and occipital cortices close to illness onset that existed before volume loss, and thus potentially provide important new insight into the early neurobiology of depression.

Activation of ß-catenin stimulated by mechanical strain and estrogen requires estrogen receptor in mesenchymal stem cells (MSCs).

BACKGROUND AND OBJECTIVES: Mechanical stimulation and hormones act via interconnected signaling pathways to influence the function of bone cells. Estrogen receptor (ER) and ß-catenin play important role in bone formation and have implicated in mechanotransduction in bone cells. To investigate the interaction between mechanotransduction and estrogenic signaling in mesenchymal stem cells (MSCs), this study examined the effect of mechanical strain and estrogen on activation of ß-catenin in MSCs, and the role of ER in response to mechanical strain and estrogen in MSCs. MATERIALS AND METHODS: MSCs were exposed to mechanical strain (2%, 1 Hz) and estrogen (100 nM). The ER inhibitor, ICI182,780 was used to assess the role of ER in activation of ß-catenin stimulated by mechanical strain and estrogen. Changes of activated ß-catenin in the nuclei were determined by immunoflourescent test. The expression of ß-catenin was detected by western blotting. RESULTS: Mechanical strain and estrogen augment, respectively, activation of ß-catenin and accumulation of activated ß-catenin in the nuclei of MSCs. Combined treatment with estrogen and mechanical strain had higher levels of activated ß-catenin than the cells exposed to mechanical strain or estrogen. After MSCs were pre-treated by ICI182,780, the level of activated ß-catenin expression induced by mechanical strain or estrogen was depressed. Meanwhile, ICI182,780 blocked effect of combined stimulation on activation of ß-catenin in MSCs. CONCLUSIONS: Our study demonstrates that mechanical strain and estrogen both promote the levels of activated ß-catenin in MSCs. Estrogen receptor implicates in activation of ß-catenin stimulation by mechanical strain and estrogen in MSCs.

Regional increases of cortical thickness in untreated, first-episode major depressive disorder.

The large majority of structural MRI studies of major depressive disorder (MDD) investigated volumetric changes in chronic medicated patients in whom course of illness and treatment effects may impact anatomic measurements. Further, in few studies, separate measurements of cortical thickness and surface area have been performed that reflect different neurobiological processes regulated by different genetic mechanisms. In the present study, we investigated both cortical thickness and surface area in first-episode, treatment-naïve, mid-life MDD to elucidate the core pathophysiology of this disease and its early impact on the brain. We observed increased cortical thickness in the right hemisphere, including medial orbitofrontal gyrus, pars opercularis, rostral middle frontal gyrus and supramarginal gyrus. Increased thickness of rostral middle frontal gyrus was negatively related with depression severity on the Hamilton Depression Rating Scale. Furthermore, MDD patients showed significantly increased associations in cortical thickness measurements among areas where increased cortical thickness was observed. Analysis of pial area revealed a trend toward increased surface area in the left parahippocampal gyrus in MDD. To permit comparison of our data with those of previous gray matter volume studies, voxel-based morphometry was performed. That analysis revealed significantly increased gray matter volume in left paracentral lobule, left superior frontal gyrus, bilateral cuneus and thalamus which form limbic-cortico-striato-pallido-thalamic loops. These changes in first-episode, treatment-naïve, mid-life MDD patients may reflect an active illness-related cortical change close to illness onset, and thus potentially provide important new insight into the early neurobiology of the disorder.

Could giant basin-forming impacts have killed Martian dynamo?

The observed strong remanent crustal magnetization at the surface of Mars suggests an active dynamo in the past and ceased to exist around early to middle Noachian era, estimated by examining remagnetization strengths in extant and buried impact basins. We investigate whether the Martian dynamo could have been killed by these large basin-forming impacts, via numerical simulation of subcritical dynamos with impact-induced thermal heterogeneity across the core-mantle boundary. We find that subcritical dynamos are prone to the impacts centered on locations within 30° of the equator but can easily survive those at higher latitudes. Our results further suggest that magnetic timing places a strong constraint on postimpact polar reorientation, e.g., a minimum 16° polar reorientation is needed if Utopia is the dynamo killer.

Role of mechanical strain and estrogen in modulating osteogenic differentiation of mesenchymal stem cells (MSCs) from normal and ovariectomized rats.

Bone's adaptability to loading depends upon the process of bone remodeling. This adaptive mechanism is restricted in postmenopausal osteoporosis. Differentiation of mesenchymal stem cells (MSCs) is crucial to bone remodeling and regeneration. It is well accepted that mechanical loading influences the fate of MSC differentiation. The aim of this study was to explore the possible restricted mechanism in osteoporotic condition, through investigating response of MSCs from both sham-operated and ovariectomized rats. MSCs were exposed to estrogen and mechanical strain (2%, 1Hz, 6h/day) for 3 days. Osteogenic differentiation and ß-catenin protein in MSCs were examined. Exposure to estrogen and mechanical strain alone enhanced expression of Runx2 (Cbfα1), type I collagen (ColI) and activated ß-catenin protein in MSCs from both sham-operated and OVX rats. MSCs from both sham-operated and OVX rats stimulated with both mechanical strain and estrogen had higher expression of osteogenic genes and activated ß-catenin protein than these cells exposed to estrogen and mechanical strain alone. Osteoporotic MSCs had lower expression of osteogenic genes and protein in the absence and presence of stimulation than did MSCs from sham-operated rats. Cumulatively, our results indicate that mechanical strain and estrogen in vitro enhance osteogenic potential and activation of ß-catenin in MSCs from both sham-operated and OVX rats. Estrogen augments strain-induced osteogenic potential and activity of ß-catenin in MSCs.

A study on the relationship between TCTA tetranucleotide polymorphism of the HPRT gene and primary hyperuricemia.

We examined polymorphism of the TCTA tetranucleotide sequence in the 3rd intron of the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene in the Han population of Ningxia Province in China. We also looked for a possible relationship between STR polymorphism in the 3rd intron of the HPRT gene and primary hyperuricemia. We used Chelex-100 to extract DNA, then PCR, PAGE and silver staining for allele genotyping and DNA sequencing to obtain the distribution of the alleles. We found, for the first time, that there is high STR polymorphism in the 3rd intron of the HPRT gene. We detected 5 STR alleles in this intron in the Han population of Ningxia Province, with 15 genotypes in females; significant differences were observed in the distribution of alleles and genotypes between control and patient groups for both males and females. Alleles of the TCTA repeat in the 3rd intron of the HPRT gene were found to be associated with primary hyperuricemia; consequently, these alleles may be considered risk factors for primary hyperuricemia.

A new single-nucleotide mutation (rs362719) of the reelin (RELN) gene associated with schizophrenia in female Chinese Han.

Reelin is an extracellular signaling protein that plays an important role in the development of the central nervous system. Post-mortem studies have shown lower reelin protein levels in the brains of patients with schizophrenia and bipolar disorder compared with controls. Genetic studies have also shown that mutations in the reelin gene (RELN) increase the risk for schizophrenia and bipolar disorder. We evaluated whether an RELN gene variant, rs362719, which has been associated with increased susceptibility to bipolar disorder, is also associated with susceptibility to schizophrenia. We included 405 Chinese Han schizophrenia patients and 390 controls in our study. The polymorphism was genotyped by PCR and RFLP methods. We found a significant difference in allele frequency distribution (P< 0.05) between schizophrenia patients and controls. The frequency of the A allele was significantly higher in schizophrenia patients than in healthy controls. The effect of SNP rs362719 on allele distribution was significant in female (P < 0.05) but not in male participants (P = 0.473). Besides the gender factor, demographic and clinical characteristics of the rs362719 genotype groups were also analyzed using the chi-square test, but no significant differences were found. We conclude that rs362719 of the RELN gene is associated with susceptibility to schizophrenia in Chinese Han, possibly through a gender-specific mechanism. Further studies will be needed to confirm this genetic risk factor for schizophrenia.