Exhaled Anesthetic Xenon Regeneration by Gas Separation Using a Metal-Organic Framework with Sorbent-Sorbate Induced-Fit.

Noble gas xenon (Xe) is an excellent anesthetic gas, but its rarity, high cost and constrained production prohibits wide use in medicine. Here, we have developed a closed-circuit anesthetic Xe recovery and reusage process with highly effective CO2-specific adsorbent CUPMOF-5 that is promising to solve the anesthetic Xe supply problem. CUPMOF-5 possesses spacious cage cavities interconnected in four directions by confinement throat apertures of ~3.4 Å, which makes it an ideal molecular sieving of CO2 from Xe, O2, N2 with the benchmark selectivity and high uptake capacity of CO2. In-situ single-crystal X-ray diffraction (SCXRD) and computational simulation solidly revealed the vital sieving role of the confined throat and the sorbent-sorbate induced-fit strengthening binding interaction to CO2. CUPMOF-5 can remove 5% CO2 even from actual moist exhaled anesthetic gases, and achieves the highest Xe recovery rate (99.8%) so far, as verified by breakthrough experiments. This endows CUPMOF-5 great potential for the on-line CO2 removal and Xe recovery from anesthetic closed-circuits.

Deterministic switching of a perpendicularly polarized magnet using unconventional spin-orbit torques in WTe2.

Spin-orbit torque (SOT)-driven deterministic control of the magnetic state of a ferromagnet with perpendicular magnetic anisotropy is key to next-generation spintronic applications including non-volatile, ultrafast and energy-efficient data-storage devices. However, field-free deterministic switching of perpendicular magnetization remains a challenge because it requires an out-of-plane antidamping torque, which is not allowed in conventional spin-source materials such as heavy metals and topological insulators due to the system's symmetry. The exploitation of low-crystal symmetries in emergent quantum materials offers a unique approach to achieve SOTs with unconventional forms. Here we report an experimental realization of field-free deterministic magnetic switching of a perpendicularly polarized van der Waals magnet employing an out-of-plane antidamping SOT generated in layered WTe2, a quantum material with a low-symmetry crystal structure. Our numerical simulations suggest that the out-of-plane antidamping torque in WTe2 is essential to explain the observed magnetization switching.

N-Heterocyclic Carbene-Catalyzed [3 + 3] Annulation of 5-Aminopyrazoles with Enals: Enantioselective Synthesis of Pyrazolo[3,4-b]pyridones.

An enantioselective construction of pyrazolo[3,4-b]pyridones was achieved via N-heterocyclic carbene-catalyzed [3 + 3] annulation of enals with 5-aminopyrazoles. This protocol not only offers a highly efficient synthetic approach for the preparation of various substituted pyrazolo[3,4-b]pyridones but also provides an effective method for the rapid synthesis of enantiopure spirooxindone derivatives.

Atroposelective Access to Dihydropyridinones with C-N Axial and Point Chirality via NHC-Catalyzed [3 + 3] Annulation.

An N-heterocyclic carbene-catalyzed atroposelective [3 + 3] annulation of enals with 2-aminomaleate derivatives is described. A series of substituted dihydropyridones bearing both C-N axis and point chirality were synthesized with good diastereo- and enantioselectivity under mild conditions. This efficient strategy successfully superpositions an extra point chiral element with an axial backbone, and the generated structurally interesting atropisomers may have potential application in drug discovery.

Chemically detaching hBN crystals grown at atmospheric pressure and high temperature for high-performance graphene devices.

In this work, we report on the growth of hexagonal boron nitride (hBN) crystals from an iron flux at atmospheric pressure and high temperature and demonstrate that (i) the entire sheet of hBN crystals can be detached from the metal in a single step using hydrochloric acid and that (ii) these hBN crystals allow to fabricate high carrier mobility graphene-hBN devices. By combining spatially-resolved confocal Raman spectroscopy and electrical transport measurements, we confirm the excellent quality of these crystals for high-performance hBN-graphene-based van der Waals heterostructures. The full width at half maximum of the graphene Raman 2D peak is as low as 16 cm-1, and the room temperature charge carrier mobilitiy is around 80 000 cm2/(Vs) at a carrier density 1 × 1012cm-12. This is fully comparable with devices of similar dimensions fabricated using crystalline hBN synthesized by the high pressure and high temperature method. Finally, we show that for exfoliated high-quality hBN flakes with a thickness between 20 and 40 nm the line width of the hBN Raman peak, in contrast to the graphene 2D line width, is not useful for benchmarking hBN in high mobility graphene devices.

Mechanism of METTL3-Mediated m6A Modification in Cardiomyocyte Pyroptosis and Myocardial Ischemia-Reperfusion Injury.

OBJECTIVE: Myocardial ischemia/reperfusion (MI/R) injury is a complicated pathophysiological process associated with cardiomyocyte pyroptosis. Methyltransferase-like protein 3 (METTL3) catalyzes the formation of N6-methyl-adenosine (m6A) and participates in various biological processes. This study probed into the mechanism of METTL3 in cardiomyocyte pyroptosis in MI/R injury. METHODS: A rat model of MI/R was established. Rat cardiomyocytes were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) treatment for the establishment of a cell model in vitro. METTL3 expression in myocardial tissues of MI/R rats and OGD/R-treated cardiomyocytes was determined using RT-qPCR and Western blot. The pathological changes of rat myocardial tissues were observed using hematoxylin and eosin staining. The positive expression of NLRP3 in myocardial tissues or cardiomyocytes was observed through immunohistochemistry or immunofluorescence. The activity of caspase-1 was measured using the colorimetric method. The expressions of GSDMD and cleaved caspase-1, as well as the levels of IL-1ß and IL-18 in rat myocardial tissues or cardiomyocytes were determined. m6A modification level was quantified. The binding relationship between pri-miR-143-3p and DGCR8 and the enrichment of m6A on pri-miR-143-3p were detected. The binding relationship between miR-143-3p and protein kinase C epsilon (PRKCE) was verified. RESULTS: METTL3 expression was elevated in MI/R rats and OGD/R cardiomyocytes. METTL3 silencing alleviated myocardial injury, reduced the number of NLRP3-positive cardiomyocytes, suppressed caspase-1 activity, decreased the protein levels of GSDMD-N and cleaved caspase-1, and decreased IL-1ß and IL-18 levels. METTL3 increased the total m6A level in MI/R rats and injured cardiomyocytes, promoted DGCR8 binding to pri-miR-143-3p, and enhanced miR-143-3p expression. miR-143-3p suppressed PRKCE transcription, and miR-143-3p overexpression reversed the inhibitory effect of METTL3 silencing on cardiomyocyte pyroptosis. CONCLUSION: METTL3 promoted DGCR8 binding to pri-miR-143-3p through m6A modification, thus enhancing miR-143-3p expression to inhibit PRKCE transcription and further aggravating cardiomyocyte pyroptosis and MI/R injury.

Joint efficacy of the three biomarkers SNCA, GYPB and HBG1 for atrial fibrillation and stroke: Analysis via the support vector machine neural network.

Atrial fibrillation (AF) is the most common type of persistent arrhythmia. Although its incidence has been increasing, the pathogenesis of AF in stroke remains unclear. In this study, a total of 30 participants were recruited, including 10 controls, 10 patients with AF and 10 patients with AF and stroke (AF + STROKE). Differentially expressed genes (DEGs) were identified, and functional annotation of DEGs, comparative toxicogenomic database analysis associated with cardiovascular diseases, and predictions of miRNAs of hub genes were performed. Using RT-qPCR, biological process and support vector machine neural networks, numerous DEGs were found to be related to AF. HBG1, SNCA and GYPB were found to be upregulated in the AF group. Higher expression of hub genes in AF and AF + STROKE groups was detected via RT-PCR. Upon training the biological process neural network of SNCA and GYPB for HBG1, only small differences were detected. Based on the support vector machine, the predicted value of SNCA and GYPB for HBG1 was 0.9893. Expression of the hub genes of HBG1, SNCA and GYPB might therefore be significantly correlated to AF. These genes are involved in the incidence of AF complicated by stroke, and may serve as targets for early diagnosis and treatment.

[Metabonomic study of biochemical changes in serum of PCPA-induced insomnia rats after treatment with Suanzaoren Decoction].

Suanzaoren Decoction(SZRD) is a classical formula for the clinical treatment of insomnia. This study analyzed the effect of SZRD on endogenous metabolites in insomnia rats based on metabonomics and thereby explored the anti-insomnia mechanism of SZRD. To be specific, DL-4-chlorophenylalanine(PCPA) was used to induce insomnia in rats. Then pathological changes of the liver and brain were observed and biochemical indexes such as 5-hydroxytryptamine(5-HT), dopamine(DA), glutamate(Glu), γ-aminobutyric acid(GABA), and norepinephrine(NE) in the hippocampus and prostaglandin D2(PGD2), tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), and IL-6 in the serum of rats were detected. On this basis, the effect of SZRD on PCPA-induced insomnia rats was preliminarily assessed. The metabolic profile of rat serum samples was further analyzed by ultra-performance liquid chromatography-quadrupole-time of flight-tandem mass spectrometry(UPLC-Q-TOF-MS/MS). Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were combined with t-test and variable importance in projection(VIP) to identify differential metabolites, and MetaboAnalyst 5.0 was employed for pathway analysis. The results showed that SZRD could improve the pathological changes of brain and liver tissues, increase the levels of neurotransmitters 5-HT, DA, and GABA in hippocampus and the level of PGD2 in hypothalamic-pituitary-adrenal axis(HPA axis), and reduce the levels of IL-1ß and TNF-α in serum of insomnia rats. Metabonomics analysis yielded 12 significantly changed potential metabolites: 5-aminovaleric acid, N-acetylvaline, L-proline, L-glutamate, L-valine, DL-norvaline, D(-)-arginine, pyroglutamic acid, 1-methylguanine, L-isoleucine, 7-ethoxy-4-methylcoumarin, and phthalic acid mono-2-ethylhexyl ester(MEHP), which were related with multiple biochemical processes including metabolism of D-glutamine and D-glutamate, metabolism of alanine, aspartate, and glutamate, metabolism of arginine and proline, arginine biosynthesis, glutathione metabolism. These metabolic changes indicated that SZRD can improve the metabolism in insomnia rats by regulating amino acid metabolism.

Revealing Nanoscale Confinement Effects on Hyperbolic Phonon Polaritons with an Electron Beam.

Hyperbolic phonon polaritons (HPhPs) in hexagonal boron nitride (hBN) enable the direct manipulation of mid-infrared light at nanometer scales, many orders of magnitude below the free-space light wavelength. High-resolution monochromated electron energy-loss spectroscopy (EELS) facilitates measurement of excitations with energies extending into the mid-infrared while maintaining nanoscale spatial resolution, making it ideal for detecting HPhPs. The electron beam is a precise source and probe of HPhPs, which allows the observation of nanoscale confinement in HPhP structures and directly extract hBN polariton dispersions for both modes in the bulk of the flake and modes along the edge. The measurements reveal technologically important nontrivial phenomena, such as localized polaritons induced by environmental heterogeneity, enhanced and suppressed excitation due to 2D interference, and strong modification of high-momenta excitations such as edge-confined polaritons by nanoscale heterogeneity on edge boundaries. The work opens exciting prospects for the design of real-world optical mid-infrared devices based on hyperbolic polaritons.

HiGwas: how to compute longitudinal GWAS data in population designs.

SUMMARY: Genome-wide association studies (GWAS), particularly designed with thousands and thousands of single-nucleotide polymorphisms (SNPs) (big p) genotyped on tens of thousands of subjects (small n), are encountered by a major challenge of p ≪ n. Although the integration of longitudinal information can significantly enhance a GWAS's power to comprehend the genetic architecture of complex traits and diseases, an additional challenge is generated by an autocorrelative process. We have developed several statistical models for addressing these two challenges by implementing dimension reduction methods and longitudinal data analysis. To make these models computationally accessible to applied geneticists, we wrote an R package of computer software, HiGwas, designed to analyze longitudinal GWAS datasets. Functions in the package encompass single SNP analyses, significance-level adjustment, preconditioning and model selection for a high-dimensional set of SNPs. HiGwas provides the estimates of genetic parameters and the confidence intervals of these estimates. We demonstrate the features of HiGwas through real data analysis and vignette document in the package. AVAILABILITY AND IMPLEMENTATION: https://github.com/wzhy2000/higwas. CONTACT: rwu@phs.psu.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Isotopic Disorder: The Prevailing Mechanism in Limiting the Phonon Lifetime in Hexagonal BN.

The phonon linewidth of isotopically controlled hexagonal boron nitride (h-BN) single crystals has been determined by Raman scattering. The scattering by isotopic mass disorder induces a phonon broadening that is largest for boron 11 fractions around 0.65. Lowest-order perturbation theory does not suffice to explain the dependence of the isotopic broadening on isotopic composition. A multiple-scattering theory based on the coherent potential approximation provides a good quantitative account of the phonon shift and broadening with isotopic composition observed in the experiments. Isotopic-disorder scattering is shown to have a prominent role in limiting the optical-phonon lifetime in h-BN.

Surface plasmons excited by multiple layer grating.

The surface plasmons that are excited by the multiple layer grating structures on the gold thin film are studied using the finite-difference time-domain method in this paper. The structure parameters' effects on the coupling enhancement of surface plasmons are examined, and the structure design guidelines are given. It is found that the distance between the grating layers and the distance between the gratings and gold thin film are the key structure parameters for better cavity resonances. To have the stronger field enhancements of the excited surface plasmons for the multilayer grating structures, it is found that the width of the gratings should be smaller for the lower grating layers. The multiple layer gratings with proper structure designs can have better performances than single layer grating structure because the cavity effects can enhance the light coupling and more light can be coupled into the surface plasmons by more layers of grating. It is found that the maximum electric field intensity for five layer grating structures can be 163% of the case of the single layer grating structure in our simulations.

Vortex energy flows generated by core-shell nanospheres.

Investigated in this paper is the interaction of light and the nanospheres composed by a dielectric core with a gold-shell cladding that causes the optical vortices inside the core and the whirlpools around the shell. Different radius ratios, dimensions and the dielectric functions of nanospheres were studied using the finite-difference time-domain method. It was found that optical vortices were most likely to occur in the regions of increased absorption cross section and reduced scattering cross section. Two optical vortices of the opposite polarity, each centered in one of the particles of a dimer are created by a nanoshell dimer. The surrounding media of a nanoshell with different dielectric functions can be used to affect the energy flows generated by core-shell nanospheres.

A model-free approach for detecting interactions in genetic association studies.

Over the past few decades, genome-wide association studies analyzed by efficient statistical procedures have successfully identified single-nucleotide polymorphisms (SNPs) that are associated with complex traits or human diseases. However, due to the overwhelming number of SNPs, most approaches have focused on additive genetic model without genome-wide SNP-SNP interactions. In this study, we propose an efficient statistical procedure in a genetic model-free framework for detecting SNPs exhibiting main genetic effects as well as epistatic interactions. Specifically, the association between phenotype and genotype is characterized by an unknown function to be estimated using nonparametric techniques, and a two-stage non-parametric independence screening procedure is proposed to sequentially identify potentially important main genetic effects and interactions. Finally, the subset of genetic predictors implied by two-stage non-parametric independence screening is analyzed by penalized regressions such as LASSO, and a final model is identified. In this framework, specific genetic model is not assumed and interactions are not only among marginally important SNPs. Therefore, SNPs that are involved in genetic regulatory networks but missed by previous studies are expected to be recognized. In simulation studies, we show that the procedure is computationally efficient and has an outstanding finite sample performance in selecting potential SNPs as well as SNP-SNP interactions. A real data analysis further indicates the importance of epistatic interactions in explaining body mass index.

Forward LASSO analysis for high-order interactions in genome-wide association study.

Previous genome-wide association study (GWAS) focused on low-order interactions between pairwise single-nucleotide polymorphisms (SNPs) with significant main effects. Little is known how high-order interactions effect, especially one among the SNPs without main effects regulates quantitative traits. Within the frameworks of linear model and generalized linear model, the LASSO with coordinate descent step can be used to simultaneously analyze thousands and thousands of SNPs for normal and discrete traits. With consideration of high-order interactions among SNPs, a huge number of genetic effects make the LASSO failing to work under the presented condition of computation. Forward LASSO analysis is, therefore, proposed to shrink most of genetic effects to be zeros stage by stage. Simulation demonstrates that our proposed method could be used instead of the LASSO method for full model in mapping high-order interactions. Application of forward LASSO method is provided to GWAS for carcass traits and meat quality traits in beef cattle.

A dynamic framework for quantifying the genetic architecture of phenotypic plasticity.

Despite its central role in the adaptation and microevolution of traits, the genetic architecture of phenotypic plasticity, i.e. multiple phenotypes produced by a single genotype in changing environments, remains elusive. We know little about the genes that underlie the plastic response of traits to the environment, their number, chromosomal locations and genetic interactions as well as environment impact on their effects. Here we review key statistical approaches for analyzing the genetic variation of phenotypic plasticity due to genotype-environment interactions and describe the implementation of a dynamic model to map specific quantitative trait loci (QTLs) that affect the gradient expression of a quantitative trait across a range of environments. This dynamic model is distinct by incorporating mathematical aspects of phenotypic plasticity into a QTL mapping framework, thereby better unraveling the quantitative attribute of trait response to the environment. By testing the curve parameters that specify environment-dependent trajectories of the trait, the model allows a series of fundamental hypotheses to be tested in a quantitative way about the interplay between gene action/interaction and environmental sensitivity. The model can also make the dynamic prediction of genetic control over phenotypic plasticity within the context of changing environments. We demonstrate the usefulness of the model by reanalyzing a QTL data set for rice, gleaning new insights into the genetic basis for phenotypic plasticity in plant height growth.

Cox regression model for dissecting genetic architecture of survival time.

Common quantitative trait locus (QTL) mapping methods fail to analyze survival traits of skewed normal distributions. As a result, some mapping methods for survival traits have been proposed based on survival analysis. Under a single QTL model, however, those methods perform poorly in detecting multiple QTLs and provide biased estimates of QTL parameters. For sparse oversaturated model used to map survival time loci, the least absolute shrinkage and selection operator (LASSO) for Cox regression model can be employed to efficiently shrink most of genetic effects to zero. Then, a few non-zero genetic effects are re-estimated and statistically tested using the standard maximum Cox partial likelihood method. Simulation shows that the proposed method has higher statistic power for QTL detection than that of the LASSO for logarithmic linear model or the interval mapping based on Cox model, although it somewhat underestimates QTL effects. Especially, computational speed of the method is very fast. An application of this method illustrates mapping main effect and interacting QTLs for heading time in the North American Barley Genome Mapping Project.

Effects of exchange correlation functional on optical permittivity of gold and electromagnetic responses.

Understanding the optical properties of nanometer-scale noble metals is important for the nanoplasmonic devices. The bulk gold and thin film are calculated by density functional theory (DFT) with LDA, PBE, and GLLBSC functionals, respectively. The GLLBSC results for bulk gold are closer to the experimental data because the GLLBSC functional has better descriptions of transition energy. The Im(ε) of thin film calculated by LDA and PBE are overestimated. The effects of DFT-based optical properties are performed by conducting electromagnetic simulations. The transmission for the gold thin film by GLLBSC is blue-shifted. The gold grating structure with the GLLBSC-based optical permittivity has strong localized streamlines of Poynting vector in the corner edges at the resonance condition.

Exploiting the role of resveratrol in rat mitochondrial permeability transition.

Resveratrol (RSV), a natural polyphenolic antioxidant, has been considered an anticarcinogenic agent as it triggers tumor cell apoptosis through activation of the mitochondrial pathway. In our study, the effects of RSV on mitochondria, especially on the mitochondrial permeability transition (MPT) process, were investigated by multiple methods. We found that RSV induced a collapse of membrane potential and matrix swelling related to MPT. We further demonstrated that Ca²âº was necessary for this RSV-induced MPT opening. In addition, RSV induced the inner membrane permeabilization to H⁺ and K⁺, the depression of respiration and changes in membrane fluidity. The results suggested that RSV-induced MPT was accompanied by mitochondrial dysfunction. But the prohibition on lipid peroxidation and different effects of low- and high-dose RSV on membrane fluidity and respiration showed that the interaction of RSV and the mitochondria could not be the result of a single simple mechanism.

Dynamic semiparametric Bayesian models for genetic mapping of complex trait with irregular longitudinal data.

Many phenomena of fundamental importance to biology and biomedicine arise as a dynamic curve, such as organ growth and HIV dynamics. The genetic mapping of these traits is challenged by longitudinal variables measured at irregular and possibly subject-specific time points, in which case nonnegative definiteness of the estimated covariance matrix needs to be guaranteed. We present a semiparametric approach for genetic mapping within the mixture-model setting by jointly modeling mean and covariance structures for irregular longitudinal data. Penalized spline is used to model the mean functions of individual quantitative trait locus (QTL) genotypes as latent variables, whereas an extended generalized linear model is used to approximate the covariance matrix. The parameters for modeling the mean-covariances are estimated by MCMC, using the Gibbs sampler and the Metropolis-Hastings algorithm. We derive the full conditional distributions for the mean and covariance parameters and compute Bayes factors to test the hypothesis about the existence of significant QTLs. We used the model to screen the existence of specific QTLs for age-specific change of body mass index with a sparse longitudinal data set. The new model provides powerful means for broadening the application of genetic mapping to reveal the genetic control of dynamic traits.