Free-space dissemination of time and frequency with 10-19 instability over 113 km.

Networks of optical clocks find applications in precise navigation1,2, in efforts to redefine the fundamental unit of the 'second'3-6 and in gravitational tests7. As the frequency instability for state-of-the-art optical clocks has reached the 10-19 level8,9, the vision of a global-scale optical network that achieves comparable performances requires the dissemination of time and frequency over a long-distance free-space link with a similar instability of 10-19. However, previous attempts at free-space dissemination of time and frequency at high precision did not extend beyond dozens of kilometres10,11. Here we report time-frequency dissemination with an offset of 6.3 × 10-20 ± 3.4 × 10-19 and an instability of less than 4 × 10-19 at 10,000 s through a free-space link of 113 km. Key technologies essential to this achievement include the deployment of high-power frequency combs, high-stability and high-efficiency optical transceiver systems and efficient linear optical sampling. We observe that the stability we have reached is retained for channel losses up to 89 dB. The technique we report can not only be directly used in ground-based applications, but could also lay the groundwork for future satellite time-frequency dissemination.

Strong Vertical Piezoelectricity and Broad-pH-Value Photocatalyst in Ferroelastic Y2Se2BrF Monolayer.

With the development of miniaturized devices, there is an increasing demand for 2D multifunctional materials. Six ferroelastic semiconductors, Y2Se2XX' (X, X' = I, Br, Cl, or F; X ≠ X') monolayers, are theoretically predicted here. Their in-plane anisotropic band structure, elastic and piezoelectric properties can be switched by ferroelastic strain. Moderate energy barriers can prevent the undesired ferroelastic switching that minor interferences produce. These monolayers exhibit high carrier mobilities (up to 104 cm2 V-1 s-1) with strong in-plane anisotropy. Furthermore, their wide bandgaps and high potential differences make them broad-pH-value and high-performance photocatalysts at pH value of 0-14. Strikingly, Y2Se2BrF possesses outstanding d33 (d33 = -405.97 pm/V), greatly outperforming CuInP2S6 by 4.26 times. Overall, the nano Y2Se2BrF is a hopeful candidate for multifunctional devices to generate a direct current and achieve solar-free photocatalysis. This work provides a new paradigm for the design of multifunctional energy materials.

FX5, a non-steroidal glucocorticoid receptor antagonist, ameliorates diabetic cognitive impairment in mice.

Diabetic cognitive impairment (DCI) is a common diabetic complication characterized by learning and memory deficits. In diabetic patients, hyperactivated hypothalamic-pituitary-adrenal (HPA) axis leads to abnormal increase of glucocorticoids (GCs), which causes the damage of hippocampal neurons and cognitive impairment. In this study we investigated the cognition-improving effects of a non-steroidal glucocorticoid receptor (GR) antagonist 5-chloro-N-[4-chloro-3-(trifluoromethyl) phenyl]thiophene-2-sulfonamide (FX5) in diabetic mice. Four weeks after T1DM or T2DM was induced, the mice were administered FX5 (20, 40 mg·kg-1·d-1, i.g.) for 8 weeks. Cognitive impairment was assessed in open field test, novel object recognition test, Y-maze test, and Morris water maze test. We showed that FX5 administration significantly ameliorated the cognitive impairments in both type 1 and 2 diabetic mice. Similar cognitive improvement was observed in diabetic mice following brain GR-specific knockdown by injecting AAV-si-GR. Moreover, AAV-si-GR injection occluded the cognition-improving effects of FX5, suggesting that FX5 functioning as a non-steroidal GR antagonist. In PA-treated primary neurons (as DCI model in vitro), we demonstrated that FX5 (2, 5, 10 µM) dose-dependently ameliorated synaptic impairment via upregulating GR/BDNF/TrkB/CREB pathway, protected against neuronal apoptosis through repressing GR/PI3K/AKT/GSK3ß-mediated tauopathy and subsequent endoplasmic reticulum stress. In LPS-treated primary microglia, FX5 dose-dependently inhibited inflammation through GR/NF-κB/NLRP3/ASC/Caspase-1 pathway. These beneficial effects were also observed in the hippocampus of diabetic mice following FX5 administration. Collectively, we have elucidated the mechanisms underlying the beneficial effects of non-steroidal GR antagonist FX5 on DCI and highlighted the potential of FX5 in the treatment of the disease.

Substrate-Controlled, One-Pot Synthesis: Access to Chiral Chroman-2-one and Polycyclic Derivatives.

Based on the appropriate choice of electrophiles, one-pot, multicomponent, enantioselective domino reactions have been realized which contain a five-step sequence and provide highly efficient access to potentially bioactive chroman-2-one derivatives as a single diastereoisomer with excellent enantioselectivities and in high yields. This new strategy could significantly improve the previous protocol by directly starting from commercial 2-hydroxybenzaldehydes rather than preformed lactols, which have to be synthesized in several additional steps.

Design, synthesis and antibacterial activity of a novel alkylide: 3-O-(3-aryl-propenyl)clarithromycin derivatives.

A series of novel 3-O-(3-aryl-propenyl)clarithromycin derivatives were designed, synthesized and evaluated for their in vitro antibacterial activities. Regioselective allylation at 3-OH was efficiently achieved in the presence of 9-oxime ether, compared with 9-keto. Most of the side chains were identified as the 3-O-(3-aryl-Z-prop-1-enyl) group, not the expected 3-O-(3-aryl-E-prop-2-enyl) group. Some derivatives of this series showed improved activities against erythromycin-resistant Staphylococcus aureus and Staphylococcus pneumoniae compared with the reference compound, clarithromycin, but weaker activities against susceptible strains.