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Iodine‐promoted direct diamination of α,β‐unsaturated ketone to form two C−N bonds has been developed starting from chalcone and secondary amine. This reaction was performed in THF at 50 °C in the presence of I2 and K2CO3. The protocol is metal‐free, operationally simple and carried out under mild conditions, providing an effective new way for directing diamination reactions. [ABSTRACT FROM AUTHOR]

The identification of viruses from negative staining transmission electron microscopy (TEM) images has mainly depended on experienced experts. Recent advances in artificial intelligence have enabled virus recognition using deep learning techniques. However, most of the existing methods only perform virus classification or semantic segmentation, and few studies have addressed the challenge of virus instance segmentation in TEM images. In this paper, we focus on the instance segmentation of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and other respiratory viruses and provide experts with more effective information about viruses. We propose an effective virus instance segmentation network based on the You Only Look At CoefficienTs backbone, which integrates the Swin Transformer, dense connections and the coordinate-spatial attention mechanism, to identify SARS-CoV-2, H1N1 influenza virus, respiratory syncytial virus, Herpes simplex virus-1, Human adenovirus type 5 and Vaccinia virus. We also provide a public TEM virus dataset and conduct extensive comparative experiments. Our method achieves a mean average precision score of 83.8 and F1 score of 0.920, outperforming other state-of-the-art instance segmentation algorithms. The proposed automated method provides virologists with an effective approach for recognizing and identifying SARS-CoV-2 and assisting in the diagnosis of viruses. Our dataset and code are accessible at https://github.com/xiaochiHNU/Virus-Instance-Segmentation-Transformer-Network. [ABSTRACT FROM AUTHOR]

The pomegranate flower is an ancient herb in traditional Chinese medicine with multiple properties. Recent studies have shown that pomegranate flower extract is beneficial, especially for hyperglycemia. In this experiment, we investigated the diastolic effect of pomegranate flower polyphenol (PFP) extract on the isolated thoracic aorta of rats in both the absence and presence of high glucose levels. Isotonic contractile forces were recorded from aortic rings (about 3 mm in length) from rats using the BL-420F Biological Function Test System. Tissues were precontracted with 60 mM KCl to obtain maximum tension under 1.0 g load for 1 hour before the balance was achieved, and the fluid was changed every 15 minutes. PFP (700 mg/L–900 mg/L) showed a concentration-dependent relaxant effect on the aortic rings; vasodilation in the endothelium-intact was significantly higher than that in the de-endothelialized segments P < 0.01 . The endothelium-dependent vasorelaxant effect of PFP was partially attenuated by K+ channel blockers, tetraethylammonium (TEA), glibenclamide (Glib), and BaCl2, as well as L-NAME (eNOS inhibitor) on the denuded endothelium artery ring. Concentration-dependent inhibition of PFP on releasing intracellular Ca2+ in the Ca2+-free solution and vasoconstriction of CaCl2 in Ca2+-free buffer plus K+ (60 mM) was observed. In addition, PFP (0.1–10 mg/L) showed significant inhibition of acetylcholine-induced endothelial-dependent relaxation in the aorta of rats in the presence of high glucose (44 mmol/L). Nevertheless, the vasodilating effect of PFP was inhibited by atropine and L-NAME. The results indicated that PFP-induced vasodilation was most likely related to the antioxidant effects through enhanced NO synthesis, as well as the blocking of K+ channels and inhibition of extracellular Ca2+ entry. In conclusion, these observations showed that PFP ameliorates vasodilation in hyperglycemic rats. Hence, our results suggest that PFP supplementation may be beneficial for hypertensive patients with diabetes. [ABSTRACT FROM AUTHOR]

Background: Remote ischemic conditioning (RIC) by brief periods of limb ischemia and reperfusion protects against ischemia–reperfusion injury. We studied the cardioprotective role of extracellular vesicles (EV)s released into the circulation after RIC and EV accumulation in injured myocardium. Methods: We used plasma from healthy human volunteers before and after RIC (pre-PLA and post-PLA) to evaluate the transferability of RIC. Pre- and post-RIC plasma samples were separated into an EV enriched fraction (pre-EV + and post-EV +) and an EV poor fraction (pre-EV- and post-EV-) by size exclusion chromatography. Small non-coding RNAs from pre-EV + and post-EV + were purified and profiled by NanoString Technology. Infarct size was compared in Sprague–Dawley rat hearts perfused with isolated plasma and fractions in a Langendorff model. In addition, fluorescently labeled EVs were used to assess homing in an in vivo rat model. (ClinicalTrials.gov, number: NCT03380663) Results: Post-PLA reduced infarct size by 15% points compared with Pre-PLA (55 ± 4% (n = 7) vs 70 ± 6% (n = 8), p = 0.03). Post-EV + reduced infarct size by 16% points compared with pre-EV + (53 ± 15% (n = 13) vs 68 ± 12% (n = 14), p = 0.03). Post-EV- did not affect infarct size compared to pre-EV- (64 ± 3% (n = 15) and 68 ± 10% (n = 16), p > 0.99). Three miRNAs (miR-16-5p, miR-144-3p and miR-451a) that target the mTOR pathway were significantly up-regulated in the post-EV + group. Labelled EVs accumulated more intensely in the infarct area than in sham hearts. Conclusion: Cardioprotection by RIC can be mediated by circulating EVs that accumulate in injured myocardium. The underlying mechanism involves modulation of EV miRNA that may promote cell survival during reperfusion. [ABSTRACT FROM AUTHOR]

Temporal lobe epilepsy is the most common drug-resistant form of epilepsy in adults. The reorganization of neural networks and the gene expression landscape underlying pathophysiologic network behavior in brain structures such as the hippocampus has been suggested to be controlled, in part, by microRNAs. To systematically assess their significance, we sequenced Argonaute-loaded microRNAs to define functionally engaged microRNAs in the hippocampus of three different animal models in two species and at six time points between the initial precipitating insult through to the establishment of chronic epilepsy. We then selected commonly up-regulated microRNAs for a functional in vivo therapeutic screen using oligonucleotide inhibitors. Argonaute sequencing generated 1.44 billion small RNA reads of which up to 82% were microRNAs, with over 400 unique microRNAs detected per model. Approximately half of the detected microRNAs were dysregulated in each epilepsy model. We prioritized commonly up-regulated microRNAs that were fully conserved in humans and designed custom antisense oligonucleotides for these candidate targets. Antiseizure phenotypes were observed upon knockdown of miR-10a-5p, miR-21a-5p, and miR-142a5p and electrophysiological analyses indicated broad safety of this approach. Combined inhibition of these three microRNAs reduced spontaneous seizures in epileptic mice. Proteomic data, RNA sequencing, and pathway analysis on predicted and validated targets of these microRNAs implicated derepressed TGF-β signaling as a shared seizure-modifying mechanism. Correspondingly, inhibition of TGFβ signaling occluded the antiseizure effects of the antagomirs. Together, these results identify shared, dysregulated, and functionally active microRNAs during the pathogenesis of epilepsy which represent therapeutic antiseizure targets [ABSTRACT FROM AUTHOR]

A dynamic model for an inclined carbon fiber reinforced polymer (CFRP) cable is established, and the linear and nonlinear dynamic behaviors are investigated in detail. The partial differential equations for both the in-plane and out-of-plane dynamics of the inclined CFRP cable are obtained by Hamilton's principle. The linear eigenvalues are explored theoretically. Then, the ordinary differential equations for analyzing the dynamic behaviors are obtained by the Galerkin integral and dimensionless treatments. The steady-state solutions of the nonlinear equations are obtained by the multiple scale method (MSM) and the Newton-Raphson method. The frequency- and force-response curves are used to investigate the dynamic behaviors of the inclined CFRP cable under simultaneous internal (between the lowest in-plane and out-of-plane modes) and external resonances, i.e., the primary resonances induced by the excitations of the in-plane mode, the out-of-plane mode, and both the in-plane mode and the out-of-plane mode, respectively. The effects of the key parameters, e.g., Young's modulus, the excitation amplitude, and the frequency on the dynamic behaviors, are discussed in detail. Some interesting phenomena and results are observed and concluded. [ABSTRACT FROM AUTHOR]

Plants contain various factors that transiently interact with subunits or intermediates of the thylakoid multiprotein complexes, promoting their stable association and integration. Hence, assembly factors are essential for chloroplast development and the transition from heterotrophic to phototrophic growth. Snowy cotyledon 2 (SCO2) is a DNAJ-like protein involved in thylakoid membrane biogenesis and interacts with the light-harvesting chlorophyll-binding protein LHCB1. In Arabidopsis thaliana , SCO2 function was previously reported to be restricted to cotyledons. Here we show that disruption of SCO2 in Lotus japonicus results not only in paler cotyledons but also in variegated true leaves. Furthermore, smaller and pale-green true leaves can also be observed in A. thaliana sco2 ( atsco2 ) mutants under short-day conditions. In both species, SCO2 is required for proper accumulation of PSII–LHCII complexes. In contrast to other variegated mutants, inhibition of chloroplastic translation strongly affects L. japonicus sco2 mutant development and fails to suppress their variegated phenotype. Moreover, inactivation of the suppressor of variegation AtClpR1 in the atsco2 background results in an additive double-mutant phenotype with variegated true leaves. Taken together, our results indicate that SCO2 plays a distinct role in PSII assembly or repair and constitutes a novel factor involved in leaf variegation. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is closely associated with abnormal deposition of amyloid β (Aβ) peptides and formation of plaques. Green fluorescent protein (GFP) chromophores with a high-quality biomimetic fluorophore skeleton, have been extensively explored in biomedical diagnosis. However, its applications in intact animals were highly limited due to their short excitations and emissions owing to the absorption, scattering and auto-fluorescence by endogenous substances. In this work, through π-extension of the double bond bridge between the aromatic and imidazolidinone rings of the GFP chromophore, the emission of CX1 reached NIR window (over 702 nm) and what's more interesting, the affinity of CX1 with Aβ aggregates was obviously improved. CX1 effectively avoided the limit in vivo imaging due to short excitation and emission and showed higher selectivity and signal-to-noise ratio towards Aβ plaques. In the hydrophobic cavity of Aβ aggregates or increased viscosity, the free rotation of CX1 was efficiently limited due to inhibition of twisted intramolecular charge transfer and thus the fluorescence emission exhibited a significant increase. Furthermore, CX1 can clearly image Aβ aggregates in the brain of transgenic mice and viscosity in living cells, which could serve as an effective tool for monitoring the pathological process of AD. [Display omitted] • A series of near-infrared GPF-based fluorescent probes have been developed for imaging amyloid-β plaque and viscosity. • CX1 exhibited the highest binding affinity with Aβ aggregates compared to other GFP derivatives. • CX1 showed an enhanced near-infrared emission over 702 nm in viscous glycerol. • CX1 can clearly image Aβ plaques in the brain of transgenic mice and cellular viscosity. • CX1 might serve as a dual-functional tool for monitoring the pathological process of AD. [ABSTRACT FROM AUTHOR]

Long terminal repeat ( LTR) retrotransposons are closely related to retroviruses, and their activities shape eukaryotic genomes. Here, we present a complete Lotus japonicus insertion mutant collection generated by identification of 640 653 new insertion events following de novo activation of the LTR element Lotus retrotransposon 1 ( LORE1) (). Insertion preferences are critical for effective gene targeting, and we exploit our large dataset to analyse LTR element characteristics in this context. We infer the mechanism that generates the consensus palindromes typical of retroviral and LTR retrotransposon insertion sites, identify a short relaxed insertion site motif, and demonstrate selective integration into CHG-hypomethylated genes. These characteristics result in a steep increase in deleterious mutation rate following activation, and allow LORE1 active gene targeting to approach saturation within a population of 134 682 L. japonicus lines. We suggest that saturation mutagenesis using endogenous LTR retrotransposons with germinal activity can be used as a general and cost-efficient strategy for generation of non-transgenic mutant collections for unrestricted use in plant research. [ABSTRACT FROM AUTHOR]