IL-17A produced by αβ T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction.

Emerging evidence suggests that the T helper 17 (T(H)17) subset of αβ T cells contributes to the development of allergic asthma. In this study, we found that mice lacking the αvβ8 integrin on dendritic cells did not generate T(H)17 cells in the lung and were protected from airway hyper-responsiveness in response to house dust mite and ovalbumin sensitization and challenge. Because loss of T(H)17 cells inhibited airway narrowing without any obvious effects on airway inflammation or epithelial morphology, we examined the direct effects of T(H)17 cytokines on mouse and human airway smooth muscle function. Interleukin-17A (IL-17A), but not IL-17F or IL-22, enhanced contractile force generation of airway smooth muscle through an IL-17 receptor A (IL-17RA)-IL-17RC, nuclear factor κ light-chain enhancer of activated B cells (NF-κB)-ras homolog gene family, member A (RhoA)-Rho-associated coiled-coil containing protein kinase 2 (ROCK2) signaling cascade. Mice lacking integrin αvβ8 on dendritic cells showed impaired activation of this pathway after ovalbumin sensitization and challenge, and the diminished contraction of the tracheal rings in these mice was reversed by IL-17A. These data indicate that the IL-17A produced by T(H)17 cells contributes to allergen-induced airway hyper-responsiveness through direct effects on airway smooth muscle

General decay projective synchronization of drive-response reaction-diffusion memristive neural networks

This paper studies the general decay projective synchronization (GDPS) of a class of drive-response reaction-diffusion memristive neural networks (RDMNNs). Firstly, a suitable controller is designed, which does not ask for any knowledge about the activation functions. Then we investigate the GDPS of drive-response RDMNNs by constructing a suitable Lyapunov functional, and an adequate condition for guaranteeing the GDPS of this type of network is inferred. Lastly, the validity of the result is demonstrated by one numerical example with simulation results

Conservation and diversification of the miR166 family in soybean and potential roles of newly identified miR166s

Identity between pre-miR166s in soybean. (TIF 5906 kb

SDSS J013127.34−-032100.1: A newly discovered radio-loud quasar at z=5.18z=5.18 with extremely high luminosity

Only very few z>5 quasars discovered to date are radio-loud, with a radio-to-optical flux ratio (radio-loudness parameter) higher than 10. Here we report the discovery of an optically luminous radio-loud quasar, SDSS J013127.34-032100.1 (J0131-0321 in short), at z=5.18+-0.01 using the Lijiang 2.4m and Magellan telescopes. J0131-0321 has a spectral energy distribution consistent with that of radio-loud quasars. With an i-band magnitude of 18.47 and radio flux density of 33 mJy, its radio-loudness parameter is ~100. The optical and near-infrared spectra taken by Magellan enable us to estimate its bolometric luminosity to be L_bol ~ 1.1E48 erg/s, approximately 4.5 times greater than that of the most distant quasar known to date. The black hole mass of J0131-0321 is estimated to be 2.7E9 solar masses, with an uncertainty up to 0.4 dex. Detailed physical properties of this high-redshift, radio-loud, potentially super-Eddington quasar can be probed in the future with more dedicated and intensive follow-up observations using multi-wavelength facilities.Comment: 5 pages, 3 figures, accepted to ApJ

Efficacy of guideline-directed medical treatment in heart failure with mildly reduced ejection fraction.

Heart failure with mildly reduced ejection fraction (HFmrEF) has received increasing attention following the publication of the latest ESC guidelines in 2021. However, it remains unclear whether patients with HFmrEF could benefit from guideline-directed medical treatment (GDMT), referring the combination of ACEI/ARB/ARNI, β-blockers, and MRAs, which are recommended for those with reduced ejection fraction. This study explored the efficacy of GDMT in HFmrEF patients. This was a retrospective cohort study of HFmrEF patients admitted to The First Affiliated Hospital of Dalian Medical University between 1 September 2015 and 30 November 2019. Propensity score matching (1:2) between patients receiving triple-drug therapy (TT) and non-triple therapy (NTT) based on age and sex was performed. The primary outcome was all cause death, cardiac death, rehospitalization from any cause, and rehospitalization due to worsening heart failure. Of the 906 patients enrolled in the matched cohort (TT group, n = 302; NTT group, N = 604), 653 (72.08%) were male, and mean age was 61.1 ± 11.92. Survival analysis suggested that TT group experienced a significantly lower incidence of prespecified primary endpoints than NTT group. Multivariable Cox regression showed that TT group had a lower risk of all-cause mortality (HR 0.656, 95% CI 0.447-0.961, P = 0.030), cardiac death (HR 0.599, 95% CI 0.380-0.946, P = 0.028), any-cause rehospitalization (HR 0.687, 95% CI 0.541-0.872, P = 0.002), and heart failure rehospitalization (HR 0.732, 95% CI 0.565-0.948, P = 0.018). In patients with HFmrEF, combined use of neurohormonal antagonists produces remarkable effects in reducing the occurrence of the primary outcome of rehospitalization and death. Thus, the treatment of HFmrEF should be categorized as HFrEF due to the similar benefit of neurohormonal blocking therapy in HFrEF and HFmrEF. [Abstract copyright: © 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Research progress of natural silk fibroin and the application for drug delivery in chemotherapies

Silk fibroin has been widely used in biological fields due to its biocompatibility, mechanical properties, biodegradability, and safety. Recently, silk fibroin as a drug carrier was developed rapidly and achieved remarkable progress in cancer treatment. The silk fibroin-based delivery system could effectively kill tumor cells without significant side effects and drug resistance. However, few studies have been reported on silk fibroin delivery systems for antitumor therapy. The advancement of silk fibroin-based drug delivery systems research and its applications in cancer therapy are highlighted in this study. The properties, applications, private opinions, and future prospects of silk fibroin carriers are discussed to understand better the development of anti-cancer drug delivery systems, which may also contribute to advancing silk fibroin innovation

Metabolism of Salvianolic Acid A and Antioxidant Activities of Its Methylated Metabolites

ABSTRACT This study investigated the metabolism of salvianolic acid A (SAA) both in vivo and in vitro. Liquid chromatography-mass spectrometry analysis of drug-containing rat bile samples and bile samples hydrolyzed by glucuronidase revealed a series of methylated conjugates of SAA and its glucuronides, as well as the predominance of the methylation pathway of SAA in rats. For the first time, four major methylated metabolites present in vivo were prepared for structure characterization and bioactivity evaluation using in vitro coincubation systems with rat hepatic cytosol protein as the enzyme donor. By using nuclear magnetic resonance imaging and other spectroscopic methods, these metabolites were unambiguously elucidated as 3-O-methyl-SAA (M1), 39-O-methyl-SAA (M2), 3,30-O-dimethyl-SAA (M3), and 39,30-O-dimethyl-SAA (M4), respectively. Along with results from the enzyme inhibition study, selective formation of these meta-O-methylated derivatives indicated that catechol O-methyltransferase (COMT) is responsible for methylated transformation of SAA. All of these metabolites displayed fairly high antioxidant potency against in vitro rat liver lipid peroxidation with halfmaximal inhibitory concentrations that were much lower than those of the positive controls and even SAA. Overall, the results from this study demonstrate that SAA is a metabolically unstable compound that undergoes rapid methylation metabolism catalyzed by COMT, and these generated O-methylated metabolites may be largely responsible for its in vivo pharmacological effects

STF-based diagnosis of AUV thruster faults

The diagnosis of thruster faults of autonomous underwater vehicles is studied in this paper. Based on the theory of strong tracking filter (STF), the AUV motion model and the thruster fault model are established. The STFs are designed for each thruster for the purpose of fault diagnosis. The AUV state and the fault deviation of the thruster are estimated online before the thruster faults are diagnosed based on residual analysis. The simulation experiments were conducted to verify the feasibility and effectiveness of the STF-based diagnosis of AUV thruster faults

Composition of soluble organic matter and its causes of No. 11 coal from Sangshuping Mine, Shaanxi Province

Eight samples of No.11 coal in Sangshuping Mine were used for organic geochemical study, Gas chromatography-mass spectrometry (GC-MS) and X-ray fluorescence spectrometry (XRF) were combined with the test results of proximate analysis, sulfur forms and random vitrinite reflectance, the organic matter sources and coal-forming environment of No.11 coal from the Sangshuping mine, Shaanxi Province were comprehensively analyzed. The results indicate that the total sulfur content of the coal sample is 3.29%, and the mean vitrinite oil-leaching reflectance is 2.01%, which is high-sulfur lean coal. The phase parameters of major elements indicate that the coal samples are mainly formed in reductive sedimentary environment. There are two types of carbon number distribution of n-alkanes in saturated hydrocarbon: the front peak type main carbon peak is C16, and the back peak type is main carbon C26; Combined with the distribution characteristics of ∑C22−/∑C23+、(C21+C22)/(C28+C29)、Pr/nC17、Ph/nC18 indicated that the parent material of organic matter come from aquatic organisms and higher plants. The OEP value was between 0.49 to 1.05,with an average value of 0.84, indicating that No.11 coal of Sangshuping has undergone different degrees of biodegradation. In the analysis of saturated hydrocarbon steroidal terpanes, the ratio of w(Ts)/w(Tm) is between 0.83-1.21 and w(Ts)/[w(Ts)+w(Tm)] is between 0.45-0.55, indicating that the thermal evolution degree of coal sample is high. In the analysis of aromatic compounds, the methyl rearrangement of trimethylnaphthalene and the distribution characteristics of methyl phenanthrene index are correlated with the high thermal evolution degree of coal samples. The aromatic hydrocarbons were dominated by naphthalene, phenanthrene and biphenyl series, and the sulfur-containing compounds in the trifluorene series (oxygen-fluorene, sulfur-fluorene, fluorene) are obviously higher than the oxygen-containing compounds, which also indicates the coal-forming environment under higher salinity partial reduction conditions