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SARS-CoV-2 has been spreading around the world for the past year. Recently, several variants such as B.1.1.7 (alpha), B.1.351 (beta), and P.1 (gamma), which share a key mutation N501Y on the receptor-binding domain (RBD), appear to be more infectious to humans. To understand the underlying mechanism, we used a cell surface-binding assay, a kinetics study, a single-molecule technique, and a computational method to investigate the interaction between these RBD (mutations) and ACE2. Remarkably, RBD with the N501Y mutation exhibited a considerably stronger interaction, with a faster association rate and a slower dissociation rate. Atomic force microscopy (AFM)-based single-molecule force microscopy (SMFS) consistently quantified the interaction strength of RBD with the mutation as having increased binding probability and requiring increased unbinding force. Molecular dynamics simulations of RBD–ACE2 complexes indicated that the N501Y mutation introduced additional π-π and π-cation interactions that could explain the changes observed by force microscopy. Taken together, these results suggest that the reinforced RBD–ACE2 interaction that results from the N501Y mutation in the RBD should play an essential role in the higher rate of transmission of SARS-CoV-2 variants, and that future mutations in the RBD of the virus should be under surveillance.

Proxy-based reconstructions and modeling of Holocene spatiotemporal precipitation patterns for China and Mongolia have hitherto yielded contradictory results indicating that the basic mechanisms behind the East Asian Summer Monsoon and its interaction with the westerly jet stream remain poorly understood. We present quantitative reconstructions of Holocene precipitation derived from 101 fossil pollen records and analyse them with the help of a minimal empirical model. We show that the westerly jet-stream axis shifted gradually southward and became less tilted since the middle Holocene. This was tracked by the summer monsoon rain band resulting in an early-Holocene precipitation maximum over most of western China, a mid-Holocene maximum in north-central and northeastern China, and a late-Holocene maximum in southeastern China. Our results suggest that a correct simulation of the orientation and position of the westerly jet stream is crucial to the reliable prediction of precipitation patterns in China and Mongolia. The basic mechanisms behind the East Asian Summer Monsoon remain poorly understood. Using proxy-based reconstructions and simulations, here the authors show that changes in the orientation and position of the westerly jet stream resulted in regionally asynchronous Holocene precipitation maxima.

The nonlinear dynamics of a two-sided collapsible channel flow is investigated by using an immersed boundary-lattice Boltzmann method. The stability of the hydrodynamic flow and collapsible channel walls is examined over a wide range of Reynolds numbers $Re$, structure-to-fluid mass ratios $M$ and external pressures $P_e$. Based on extensive simulations, we first characterise the chaotic behaviours of the collapsible channel flow and explore possible routes to chaos. We then explore the physical mechanisms responsible for the onset of self-excited oscillations. Nonlinear and rich dynamic behaviours of the collapsible system are discovered. Specifically, the system experiences a supercritical Hopf bifurcation leading to a period-1 limit cycle oscillation. The existence of chaotic behaviours of the collapsible channel walls is confirmed by a positive dominant Lyapunov exponent and a chaotic attractor in the velocity-displacement phase portrait of the mid-point of the collapsible channel wall. Chaos in the system can be reached via period-doubling and quasi-periodic bifurcations. It is also found that symmetry breaking is not a prerequisite for the onset of self-excited oscillations. However, symmetry breaking induced by mass ratio and external pressure may lead to a chaotic state. Unbalanced transmural pressure, wall inertia and shear layer instabilities in the vorticity waves contribute to the onset of self-excited oscillations of the collapsible system. The period-doubling, quasi-periodic and chaotic oscillations are closely associated with vortex pairing and merging of adjacent vortices, and interactions between the vortices on the upper and lower walls downstream of the throat.

Fish adaption behaviors in complex environments are of great importance in improving the performance of underwater vehicles. This work presents a numerical study of the adaption behaviors of self-propelled fish in complex environments by developing a numerical framework of deep learning and immersed boundary–lattice Boltzmann method (IB–LBM). In this framework, the fish swimming in a viscous incompressible flow is simulated with an IB–LBM which is validated by conducting two benchmark problems including a uniform flow over a stationary cylinder and a self-propelled anguilliform swimming in a quiescent flow. Furthermore, a deep recurrent Q-network (DRQN) is incorporated with the IB–LBM to train the fish model to adapt its motion to optimally achieve a specific task, such as prey capture, rheotaxis and Kármán gaiting. Compared to existing learning models for fish, this work incorporates the fish position, velocity and acceleration into the state space in the DRQN; and it considers the amplitude and frequency action spaces as well as the historical effects. This framework makes use of the high computational efficiency of the IB–LBM which is of crucial importance for the effective coupling with learning algorithms. Applications of the proposed numerical framework in point-to-point swimming in quiescent flow and position holding both in a uniform stream and a Kármán vortex street demonstrate the strategies used to adapt to different situations.

Quantum key distribution (QKD)1,2 offers a long-term solution to secure key exchange. Due to photon loss in transmission, it was believed that the repeaterless key rate is bounded by a linear function of the transmittance, O(η) (refs. 3,4), limiting the maximal secure transmission distance5,6. Recently, a novel type of QKD scheme has been shown to beat the linear bound and achieve a key rate performance of O(η) (refs. 7–9). Here, by employing the laser injection technique and the phase post-compensation method, we match the modes of two independent lasers and overcome the phase fluctuation. As a result, the key rate surpasses the linear bound via 302 km and 402 km commercial-fibre channels, over four orders of magnitude higher than existing results5. Furthermore, our system yields a secret key rate of 0.118 bps with a 502 km ultralow-loss fibre. This new type of QKD pushes forward long-distance quantum communication for the future quantum internet.Phase-matching quantum key distribution is implemented with a 502 km ultralow-loss optical fibre. The fluctuations of the laser initial phases and frequencies are suppressed by the laser injection technique and the phase post-compensation method.

This paper presents a DSD/SST study of the hydrodynamic effects of mucus on swimming performance of an undulatory foil in a non-Newtonian uniform flow. As the non-Newtonian effects are dominant in the boundary layer, this model can be taken as a simple strategy to study the hydrodynamic effects of fish mucus. Based on the simulations by varying the power-law fluid behavior index, some propulsive properties including the drag coefficients, the power coefficients, and the flow fields are analyzed in detail. It is found that in addition to other biological functions, the fish mucus serves to reduce the friction, enhance the thrust, save hydrodynamic power, reduce the force oscillations, and reduce the swimming sound. This work provides a better understanding of the fish mucus effects from the point of view of hydrodynamics.

For any given integer r ⩾ 3 , let k = k ( n ) be an integer with r ⩽ k ⩽ n . A hypergraph is r -uniform if each edge is a set of r vertices, and is said to be linear if two edges intersect in at most one vertex. Let A 1 , … , A k be a given k -partition of [ n ] with | A i | = n i ⩾ 1 . An r -uniform hypergraph H is called k - partite if each edge e satisfies | e ∩ A i | ⩽ 1 for 1 ⩽ i ⩽ k . In this paper, the number of linear k -partite r -uniform hypergraphs on n → ∞ vertices is determined asymptotically when the number of edges is m ( n ) = o ( n 4 3 ) . For k = n , it is the number of linear r -uniform hypergraphs on vertex set [ n ] with m = o ( n 4 3 ) edges.

Aircraft with bio-inspired flapping wings that are operated in low-density atmospheric environments encounter unique challenges associated with the low density. The low density results in the requirement of high operating velocities of aircraft to generate sufficient lift resulting in significant compressibility effects. Here, we perform numerical simulations to investigate the compressibility effects on the lift generation of a bio-inspired wing during hovering flight using an immersed boundary method. The aim of this study is to develop a scaling law to understand how the lift is influenced by the Reynolds and Mach numbers, and the associated flow physics. Our simulations have identified a critical Mach number of approximately $0.6$ defined by the average wing-tip velocity. When the Mach number is lower than 0.6, compressibility does not have significant effects on the lift or flow fields, while when the Mach number is greater than $0.6$, the lift coefficient decreases linearly with increasing Mach number, due to the drastic change in the pressure on the wing surface caused by unsteady shock waves. Moreover, the decay rate is dependent on the Reynolds number and the angle of attack. Based on these observations, we propose a scaling law for the lift of a hovering flapping wing by considering compressible and viscous effects, with the scaled lift showing excellent collapse.

Osteoarthritis (OA) is a chronic, debilitating joint disease characterized by progressive destruction of articular cartilage. For a long time, OA has been considered as a degenerative disease, while recent observations indicate the mechanisms responsible for the pathogenesis of OA are multifaceted. Aging is a key factor in its development. Current treatments are palliative and no disease modifying anti-osteoarthritis drugs (DMOADs) are available. In addition to articular cartilage degradation, cellular senescence, synovial inflammation, and epigenetic alterations may all have a role in its formation. Accumulating data demonstrate a clear relationship between the senescence of articular chondrocytes and OA formation and progression. Inhibition of cell senescence may help identify new agents with the properties of DMOADs. Several anti-cellular senescence strategies have been proposed and these include sirtuin-activating compounds (STACs), senolytics, and senomorphics drugs. These agents may selectively remove senescent cells or ameliorate their harmful effects. The results from preclinical experiments and clinical trials are inspiring. However, more studies are warranted to confirm their efficacy, safety profiles and adverse effects of these agents.

Osteoporosis (OP) is a chronic bone disease characterized by aberrant microstructure and macrostructure of bone, leading to reduced bone mass and increased risk of fragile fractures. Anti-resorptive drugs, especially, bisphosphonates, are currently the treatment of choice in most developing countries. However, they do have limitations and adverse effects, which, to some extent, helped the development of anabolic drugs such as teriparatide and romosozumab. In patients with high or very high risk for fracture, sequential or combined therapies may be considered with the initial drugs being anabolic agents. Great endeavors have been made to find next generation drugs with maximal efficacy and minimal toxicity, and improved understanding of the role of different signaling pathways and their crosstalk in the pathogenesis of OP may help achieve this goal. Our review focused on recent progress with regards to the drug development by modification of Wnt pathway, while other pathways/molecules were also discussed briefly. In addition, new observations made in recent years in bone biology were summarized and discussed for the treatment of OP.