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Sporadic or late-onset Alzheimer’s disease (LOAD) accounts for more than 95% of Alzheimer’s disease (AD) cases without any family history. Although genome-wide association studies have identified associated risk genes and loci for LOAD, numerous studies suggest that many adverse environmental factors, such as social isolation, are associated with an increased risk of dementia. However, the underlying mechanisms of social isolation in AD progression remain elusive. In the current study, we found that 7 days of social isolation could trigger pattern separation impairments and presynaptic abnormalities of the mossy fibre-CA3 circuit in AD mice. We also revealed that social isolation disrupted histone acetylation and resulted in the downregulation of 2 dentate gyrus (DG)-enriched miRNAs, which simultaneously target reticulon 3 (RTN3), an endoplasmic reticulum protein that aggregates in presynaptic regions to disturb the formation of functional mossy fibre boutons (MFBs) by recruiting multiple mitochondrial and vesicle-related proteins. Interestingly, the aggregation of RTN3 also recruits the PP2A B subunits to suppress PP2A activity and induce tau hyperphosphorylation, which, in turn, further elevates RTN3 and forms a vicious cycle. Finally, using an artificial intelligence-assisted molecular docking approach, we determined that senktide, a selective agonist of neurokinin3 receptors (NK3R), could reduce the binding of RTN3 with its partners. Moreover, application of senktide in vivoeffectively restored DG circuit disorders in socially isolated AD mice. Taken together, our findings not only demonstrate the epigenetic regulatory mechanism underlying mossy fibre synaptic disorders orchestrated by social isolation and tau pathology but also reveal a novel potential therapeutic strategy for AD.

Dual-comb spectroscopy (DCS) provides broadband, high-resolution, high-sensitivity amplitude and phase spectra within a short measurement time, thus holding promises for atmospheric spectroscopy. However, previous research has been limited to measuring over open-air paths of about 20 km. Here, by developing a bistatic set-up using time–frequency dissemination and high-power optical frequency combs, we implement DCS over a 113 km turbulent horizontal open-air path. We successfully measure the absorbance spectra of CO2and H2O with a 7 nm spectral bandwidth and a 10 kHz frequency accuracy, and achieve a sensing precision of <2 ppm in 5 min and <0.6 ppm in 36 min for CO2. We anticipate our system to find immediate applications in the monitoring of urban greenhouse gas and gaseous pollutants emission. Our technology may also be extended to satellite-based DCS for greenhouse gas monitoring and calibration measurements.

Networks of optical clocks find applications in precise navigation1,2, in efforts to redefine the fundamental unit of the ‘second’3–6and in gravitational tests7. As the frequency instability for state-of-the-art optical clocks has reached the 10−19level8,9, 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 × 10−19and an instability of less than 4 × 10−19at 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.

Microwave-based satellite–ground links are used to transfer time and frequency in various applications such as metrology, navigation, positioning, and very long baseline interferometers. The existing approaches, however, cannot fully satisfy the requirements of these applications. In this study, we investigated the possibility of an optical-based satellite–ground link, where the transferred carriers are pulsed lasers, resulting in a link with a high time resolution and a large ambiguous range. First, we analyzed the parameters of satellites in different orbits and concluded that high-orbit links enable more stable time–frequency comparison or dissemination by taking advantage of the long duration, a large common view range, and the lower relativistic effects. Subsequently, we performed a 16 km free-space transfer experiment to simulate links in the loss, noise, and delay effects. The link exhibits an instability of 4×10^−18 at 3,000 s and an approximately 10 fs time deviation with an average loss of 72 dB, corresponding to the loss of a satellite–ground link at geostationary earth orbit (GEO). Based on these results, we expect that the instability of the time–frequency transfer via a GEO link might reach 10^−18 at 10,000 s.

Quantum key distribution (QKD) uses individual light quanta in quantum superposition states to guarantee unconditional communication security between distant parties. However, the distance over which QKD is achievable has been limited to a few hundred kilometres, owing to the channel loss that occurs when using optical fibres or terrestrial free space that exponentially reduces the photon transmission rate. Satellite-based QKD has the potential to help to establish a global-scale quantum network, owing to the negligible photon loss and decoherence experienced in empty space. Here we report the development and launch of a low-Earth-orbit satellite for implementing decoy-state QKD—a form of QKD that uses weak coherent pulses at high channel loss and is secure because photon-number-splitting eavesdropping can be detected. We achieve a kilohertz key rate from the satellite to the ground over a distance of up to 1,200 kilometres. This key rate is around 20 orders of magnitudes greater than that expected using an optical fibre of the same length. The establishment of a reliable and efficient space-to-ground link for quantum-state transmission paves the way to global-scale quantum networks.

Aiming at the precision generating cutting problem of rectangle spline shaft, the multi-parameter fusion method to modified cutting edge of rectangle spline hob is presented. The method based on the analysis of workpiece machining errors to establish a fusion model about the rectangle spline hob cutting parameters and the rectangle spline shaft deformation quantity, the model can indicate the connection between rectangle spling hob theoretics profile and actual cutting profile, therefore, the rectangle spline hob’s profile is modified and to simulate by polynomials. The simulation experiment indicates that the method exact approximation the hob’s modified profile. Compare with the methods of the double-circular-arc and the least square fitting, the multi-parameter fusion method can enhance both design precision and design efficiency.

To observe the curative effect of combined Chinese medicine, acupuncture and rehabilitation therapy on vascular dementia (VD), and to compare the Western medicine piracetam.

Abstract: Numerical experiments were carried out to evaluate the physical effects of upwelling/downwelling on the suspended sediment concentration (SSC) on continental shelves. The results show that (1) because the upwelling or downwelling velocity tends to be of the same order of magnitude as the settling velocity of suspended sediment, various SSC distribution patterns are possible, depending on the relative importance of the velocities; (2) the presence of upwelling can enhance the SSC; and (3) in an upwelling/downwelling system, maximum concentrations may be situated in the middle of the water column, if the settling velocity is larger than the upwelling velocity. Hence, the physical processes associated with upwelling/downwelling are relevant to the SSC distribution observed over the mud patch near Cheju Island, East China Sea. Furthermore, a qualitative analysis indicates that the presence of upwelling/downwelling in the overlying water column increases the accumulation rate at the seabed.

Residual cell-intrinsic innate immunity in cancer cells hampers infection with oncolytic viruses. Translational control of mRNA is an important feature of innate immunity, yet the identity of translationally regulated mRNAs functioning in host defense remains ill-defined. We report the translatomes of resistant murine “4T1” breast cancer cells infected with three of the most clinically advanced oncolytic viruses: herpes simplex virus 1, reovirus, and vaccinia virus. Common among all three infections are translationally de-repressed mRNAs, including Inpp5e, encoding an inositol 5-phosphatase that modifies lipid second messenger signaling. We find that viral infection induces the expression of an Inpp5emRNA variant that lacks repressive upstream open reading frames (uORFs) within its 5′ leader and is efficiently translated. Furthermore, we show that INPP5E contributes to antiviral immunity by altering virus attachment. These findings uncover a role for translational control through alternative 5′ leader expression and assign an antiviral function to the ciliopathy gene Inpp5e.