Theoretical Study on the Mechanism of Stereoselective Synthesis of Oxazolidinones

Oxazolidinones can be synthesized through an organocatalytic cascade reaction of stable sulfur ylides and nitro-olefins. This process, sequentially catalyzed by thiourea and <i>N</i>,<i>N</i>-di­methyl­amino­pyridine (DMAP), is theoretically studied using density functional theory by the continuum solvation model. It is shown that the rate- and stereoselectivity-determining step is the addition reaction of sulfur ylide to the nitro-olefin with two competing reaction channels. One channel is where the nitro-cyclo­propane is generated first and then converted into isoxazoline <i>N</i>-oxide through a DMAP-catalyzed rearrangement. The other channel is the direct generation of the isoxazoline <i>N</i>-oxide intermediate. DMAP plays an important role in the reaction as a nucleophilic catalyst. The mechanism for the important rearrangement reaction proposed by Xiao et al. (<i>J. Am. Chem. Soc.</i> <b>2008</b>, <i>130</i>, 6946–6948) is not appropriate as the reaction energy barrier is too high; a 10-step mechanism determined by our theoretical calculations is more feasible as the energy barrier is becoming much less than that by Xiao. It is the first time that the Hofmann rearrangement involved in the cascade organo­catalysis is confirmed by theoretical calculations. Our result of the stereo­selectivity for the synthesis of oxazolidi­nones is in good agreement with the experiment

A Unified Inference for Predictive Quantile Regression

The asymptotic behavior of quantile regression inference becomes dramatically different when it involves a persistent predictor with zero or nonzero intercept. Distinguishing various properties of a predictor is empirically challenging. In this paper, we develop a unified predictability test for quantile regression regardless of the presence of intercept and persistence of a predictor. The developed test is a novel combination of data splitting, weighted inference, and a random weighted bootstrap method. Monte Carlo simulations show that the new approach displays significantly better size and power performance than other competing methods in various scenarios, particularly when the predictive regressor contains a nonzero intercept. In an empirical application, we revisit the quantile predictability of the monthly S&P 500 returns between 1980 and 2019.</p

Statistical Inference for a Relative Risk Measure

<p>For monitoring systemic risk from regulators’ point of view, this article proposes a relative risk measure, which is sensitive to the market comovement. The asymptotic normality of a nonparametric estimator and its smoothed version is established when the observations are independent. To effectively construct an interval without complicated asymptotic variance estimation, a jackknife empirical likelihood inference procedure based on the smoothed nonparametric estimation is provided with a Wilks type of result in case of independent observations. When data follow from AR-GARCH models, the relative risk measure with respect to the errors becomes useful and so we propose a corresponding nonparametric estimator. A simulation study and real-life data analysis show that the proposed relative risk measure is useful in monitoring systemic risk.</p

Designed Functional Systems for High-Performance Lithium-Ion Batteries Anode: From Solid to Hollow, and to Core–Shell NiCo₂O₄ Nanoparticles Encapsulated in Ultrathin Carbon Nanosheets

Binary metal oxides have been considered as ideal and promising anode materials, which can ameliorate and enhance the electrochemical performances of the single metal oxides, such as electronic conductivity, reversible capacity, and structural stability. In this research, we report a rational method to synthesize some novel sandwich-like NiCo₂O₄@C nanosheets arrays for the first time. The nanostructures exhibit the unique features of solid, hollow, and even core–shell NiCo₂O₄ nanoparticles encapsulated inside and a graphitized carbon layers coating outside. Compared to the previous reports, these composites demonstrate more excellent electrochemical performances, including superior rate capability and excellent cycling capacity. Therefore, the final conclusion would be given that these multifarious sandwich-like NiCo₂O₄@C composites could be highly qualified candidates for lithium-ion battery anodes in some special field, in which good capability and high capacity are urgently required

Data_Sheet_1_Stochastic factors drive dynamics of ammonia-oxidizing archaeal and bacterial communities in aquaculture pond sediment.DOCX

Ammonia-oxidizing archaea (AOA) and bacteria (AOB) play an important role in nitrification, which is essential in the global nitrogen cycle. However, their dynamics and the underlying community processes in agricultural ecosystems under disturbance remain largely unknown. In this study we examined the spatiotemporal dynamics of AOA and AOB communities and analyzed their community processes in the sediment of aquaculture ponds across three different areas in China. We found some significant temporal changes in AOA and AOB community diversity and abundances, but no temporal changes in community composition, despite the significant variations in sediment properties between different sampling times. Nevertheless, significant differences were found for AOA and AOB communities between different areas. Distinct area-specific taxa were detected, and they were found to be important in determining the response of AOA and AOB communities to environmental factors. In addition, geographic distance was found to be significantly correlated with AOA and AOB community composition, which demonstrates that dispersal limitation could significantly contribute to the variations in AOA and AOB communities, and stochastic processes were found to be important in structuring AOA/AOB communities in aquaculture ponds. Taken together, our study indicates that the dynamics of AOA and AOB are based on their community characteristics in aquaculture pond sediment. Our results, for the first time, provide evidence for the dynamics of AOA and AOB communities being driven by stochastic factors in a disturbed environment, and might also be of use in the management of the aquaculture environment.</p

HGF and Direct Mesenchymal Stem Cells Contact Synergize to Inhibit Hepatic Stellate Cells Activation through TLR4/NF-kB Pathway

<div><h3>Aims</h3><p>Bone marrow-derived mesenchymal stem cells (BMSCs) can reduce liver fibrosis. Apart from the paracrine mechanism by which the antifibrotic effects of BMSCs inhibit activated hepatic stellate cells (HSCs), the effects of direct interplay and juxtacrine signaling between the two cell types are poorly understood. The purpose of this study was to explore the underlying mechanisms by which BMSCs modulate the function of activated HSCs.</p> <h3>Methods</h3><p>We used BMSCs directly and indirectly co-culture system with HSCs to evaluate the anti-fibrosis effect of BMSCs. Cell proliferation and activation were examined in the presence of BMSCs and HGF. c-met was knockdown in HSCs to evaluate the effect of HGF secreted by BMSCs. The TLR4 and Myeloid differentiation primary response gene 88(MyD88) mRNA levels and the NF-kB pathway activation were determined by real-time PCR and western blotting analyses. The effect of BMSCs on HSCs activation was investigated in vitro in either MyD88 silencing or overexpression in HSCs. Liver fibrosis in rats fed CCl₄ with and without BMSCs supplementation was compared. Histopathological examinations and serum biochemical tests were compared between the two groups.</p> <h3>Results</h3><p>BMSCs remarkably inhibited the proliferation and activation of HSCs by interfering with LPS-TLR4 pathway through a cell–cell contact mode that was partially mediated by HGF secretion. The NF-kB pathway is involved in HSCs activation inhibition by BMSCs. MyD88 over expression reduced the BMSC inhibition of NF-kB luciferase activation. BMSCs protected liver fibrosis in vivo.</p> <h3>Conclusion</h3><p>BMSCs modulate HSCs in vitro via TLR4/MyD88/NF-kB signaling pathway through cell–cell contact and secreting HGF. BMSCs have therapeutic effects on cirrhosis rats. Our results provide new insights into the treatment of hepatic fibrosis with BMSCs.</p> </div

BMSC inhibited LPS induced activation of LX2 and upregulation of TLR4.

<p>(A) The effect of different dose of LPS on LX2 cells activation as the IL-8 and TGF-β secretion. All data are shown as mean ± SD from three independent experiments. * P<0.05. (B) Relative mRNA expression of TLR4 in LX2 cells and two HSCs in response to LPS. Data are depicted relative to expression in cells without LPS, which are assigned a value of 1. (C) RT-PCR analysis of the HSC activation marker α-SMA, Col-1 and TLR4 in the indicated treatments. (D) Western blot analysis of the HSC activation marker α-SMA, Col-1 and TLR4 in the indicated treatments. Expression levels were normalized with GAPDH.</p

Primary Cells morphology and molecular expression.

<p>(A) HSC cell line LX2 (left) and GFP labeled LX2 (right). (B) BMSCs were separated from bone marrow and purified by removing the non-adherent cells at least three times. The 3rd generation BMSCs (medium) were fusiform and fibroblast-like (100×). Primary human HSC (right). (C) FCM analysis showed that the 3rd generation BMSCs expressed CD44 and CD90 but not CD45 or CD34.</p

HGF is the major cytokine involved in BMSC-mediated inhibition of LX2 activation.

<p>(A) Relative mRNA expression of Col-1 and α-SMA in LX2 with different cytokine stimulation. Data are depicted relative to expression in LX2 cells cultured with PBS, which are assigned a value of 1. All data are shown as mean ± SD from three independent experiments. * P<0.05. (B) Western blot analysis for TLR4 expression under different combination of cytokine. GAPDH was used as a loading control for all Western blots (C) Knockdown of c-met in two specific shRNA-transduced LX2 cell lines. (D) Western blot analysis for Col-1 and α-SMA expression in LX2 with c-met knockdown.</p

Targeted delivery of microRNA 146b mimic to hepatocytes by lactosylated PDMAEMA nanoparticles for the treatment of NAFLD

<p>Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, and precision therapeutic will be a benefit for the NAFLD regression. In this study, we observed low microRNA 146 b (miR-146 b) expression in NAFLD mice model induced by methionine–choline-deficient diet (MCD) compared with control group. Furthermore, miR-146b^−/− mice induced MCD exhibited severe liver steatosis and hepatitis. A bio-distribution study showed that novel Lactosylated PDMAEMA nanoparticles effectively targeted hepatocytes Lac-PDMAEMA. We coupled miR-146b mimic with Lac-PDMAEMA and then were administrated to NAFLD mice model, which could obviously alleviate the hepatic steatosis. Lac-PDMAEMA effectively delivered miR-146b mimic to hepatocytes with a ∼8-fold upregulation of miR-146b mimic targeting MyD88 and IRAK1, and in turn suppressed the expression of PPARγ. Meanwhile, TNF-α and IL-6 mRNA levels were decreased after administration of Lac-PDMAEMA/miR-146b mimic. So, we made a conclusion that targeted delivering miR-146b mimic to the hepatocytes by, coupling Lac-PDMAEMA nanoparticles could effectively alleviate the hepatic steatosis in NAFLD mice, which maybe bring a new and effective way to intervene and therapy the NAFLD.</p