Nature Communications最新文献

The sinoatrial node regulates the heart rate throughout life. Failure of this primary pacemaker results in life-threatening, slow heart rhythm. Despite its critical function, the cellular and molecular composition of the human sinoatrial node is not resolved. Particularly, no cell surface marker to identify and isolate sinoatrial node pacemaker cells has been reported. Here we use single-nuclei/cell RNA sequencing of fetal and human pluripotent stem cell-derived sinoatrial node cells to reveal that they consist of three subtypes of pacemaker cells: Core Pacemaker, Sinus Venosus, and Transitional Cells. Our study identifies a host of sinoatrial node pacemaker markers including MYH11, BMP4, and the cell surface antigen CD34. We demonstrate that sorting for CD34⁺ cells from stem cell differentiation cultures enriches for sinoatrial node cells exhibiting a functional pacemaker phenotype. This sinoatrial node pacemaker cell surface marker is highly valuable for stem cell-based disease modeling, drug discovery, cell replacement therapies, and the targeted delivery of therapeutics to sinoatrial node cells in vivo using antibody-drug conjugates.

Cobalt is an efficient catalyst for Fischer−Tropsch synthesis (FTS) of hydrocarbons from syngas (CO + H₂) with enhanced selectivity for long-chain hydrocarbons when promoted by Manganese. However, the molecular scale origin of the enhancement remains unclear. Here we present an experimental and theoretical study using model catalysts consisting of crystalline CoMnO_x nanoparticles and thin films, where Co and Mn are mixed at the sub-nm scale. Employing TEM and in-situ X-ray spectroscopies (XRD, APXPS, and XAS), we determine the catalyst’s atomic structure, chemical state, reactive species, and their evolution under FTS conditions. We show the concentration of CH_x, the key intermediates, increases rapidly on CoMnO_x, while no increase occurs without Mn. DFT simulations reveal that basic O sites in CoMnO_x bind hydrogen atoms resulting from H₂ dissociation on Co⁰ sites, making them less available to react with CH_x intermediates, thus hindering chain termination reactions, which promotes the formation of long-chain hydrocarbons.

Bubbles are ubiquitous in many research applications ranging from ultrasound imaging and drug delivery to the understanding of volcanic eruptions and water circulation in vascular plants. From an acoustic perspective, bubbles are resonant scatterers with remarkable properties, including a large scattering cross-section and strongly sub-wavelength dimensions. While it is known that the resonance properties of bubbles depend on their local environment, it remains challenging to probe this interaction at the single-bubble level due to the difficulty of manipulating a single resonating bubble in a liquid. Here, we confine a cubic bubble inside a cage using 3D printing technology, and we use this bubble as a local probe to perform scanning near-field acoustic microscopy—an acoustic analog of scanning near-field optical microscopy. By probing the acoustic interaction between a single resonating bubble and its local environment, we demonstrate near-field imaging of complex structures with a resolution that is two orders of magnitudes smaller than the wavelength of the acoustic field. As a potential application, our approach paves the way for the development of low-cost acoustic microscopes based on caged bubbles.

Time-resolved serial crystallography at X-ray Free Electron Lasers offers the opportunity to observe ultrafast photochemical reactions at the atomic level. The technique has yielded exciting molecular insights into various biological processes including light sensing and photochemical energy conversion. However, to achieve sufficient levels of activation within an optically dense crystal, high laser power densities are often used, which has led to an ongoing debate to which extent photodamage may compromise interpretation of the results. Here we compare time-resolved serial crystallographic data of the bacteriorhodopsin K-intermediate collected at laser power densities ranging from 0.04 to 2493 GW/cm² and follow energy dissipation of the absorbed photons logarithmically from picoseconds to milliseconds. Although the effects of high laser power densities on the overall structure are small, in the upper excitation range we observe significant changes in retinal conformation and increased heating of the functionally critical counterion cluster. We compare light-activation within crystals to that in solution and discuss the impact of the observed changes on bacteriorhodopsin biology.

This work describes estimation of yields of complex, multicomponent reactions (MCRs) based on the modeled networks of mechanistic steps spanning both the main reaction pathway as well as immediate and downstream side reactions. Because experimental values of the kinetic rate constants for individual mechanistic transforms are extremely sparse, these constants are approximated here using Mayr’s nucleophilicity and electrophilicity parameters fine-tuned by correction terms grounded in linear free-energy relationships. With this formalism, the model trained on the mechanistic networks of only 20 – but mechanistically- and yield-diverse MCRs – transfers well to newly discovered MCRs that are based on markedly different mechanisms and types of individual mechanistic transforms. These results suggest that mechanistic-level approach to yield estimation may be a useful alternative to models that are derived from full-reaction data and lack information about yield-lowering side reactions.

Hydrogen sulfide (H₂S) is an important endogenous gasotransmitter, but the bioorthogonal reaction triggered H₂S donors are still rare. Here we show one type of bioorthogonal H₂S donors, sydnthiones (1,2,3-oxadiazol-3-ium-5-thiolate derivatives), which was designed with the aid of density functional theory (DFT) calculations. The reactions between sydnthiones and strained alkynes provide a platform for controllable, tunable and mitochondria-targeted release of H₂S. We investigate the reactivity of sydnthiones‒dibenzoazacyclooctyne (DIBAC) reactions and their orthogonality with two other bioorthogonal cycloaddition pairs: tetrazine‒norbornene (Nor) and tetrazine‒monohydroxylated cyclooctyne (MOHO). By taking advantage of these mutually orthogonal reactions, we can realize selective labeling or drug release. Furthermore, we explore the role of H₂S, which is released from the sydnthione-DIBAC reaction, on doxorubicin-induced cytotoxicity. The results demonstrate that the viability of H9c2 cells can be significantly improved by pretreating with sydnthione 1b and DIBAC for 6 h prior to exposure to Dox.

The effective control of atomic coherence with cold atoms has made atom interferometry an essential tool for quantum sensors and precision measurements. The performance of these interferometers is closely related to the operation of large wave packet separations. We present here a novel approach for atomic beam splitters based on the stroboscopic stabilization of quantum states in an accelerated optical lattice. The corresponding Floquet state is generated by optimal control protocols. In this way, we demonstrate an unprecedented Large Momentum Transfer (LMT) interferometer, with a momentum separation of 600 photon recoils (600 ℏk) between its two arms. Each LMT beam splitter is realized in a remarkably short time (2 ms) and is highly robust against the initial velocity dispersion of the wave packet and lattice depth fluctuations. Our study shows that Floquet engineering is a promising tool for exploring new frontiers in quantum physics at large scales, with applications in quantum sensing and testing fundamental physics.

In sub-Saharan Africa, children with severe malnutrition (SM) and HIV have substantially worse outcomes than children with SM alone, facing higher mortality risk and impaired nutritional recovery post-hospitalisation. Biological mechanisms underpinning this risk remain incompletely understood. This case-control study nested within the CHAIN cohort in Kenya, Uganda, Malawi, and Burkina Faso examined effect of HIV on six months post-discharge growth among children with SM and those at risk of malnutrition, assessed proteomic signatures associated with HIV in these children, and investigated how these systemic processes impact post-discharge growth in children with SM. Using SomaScan^TM assay, 7335 human plasma proteins were quantified. Linear mixed models identified HIV-associated biological processes and their associations with post-discharge growth. Using structural equation modelling, we examined directed paths explaining how HIV influences post-discharge growth. Here, we show that at baseline, HIV is associated with lower anthropometry. Additionally, HIV is associated with protein profiles indicating increased complement activation and decreased insulin-like growth factor signalling and bone mineralisation. HIV indirectly affects post-discharge growth by influencing baseline anthropometry and modulating proteins involved in bone mineralisation and humoral immune responses. These findings suggest specific biological pathways linking HIV to poor growth, offering insights for targeted interventions in this vulnerable population.

Nonlinear optical responses in two-dimensional (2D) materials can build free-space optical neuromorphic computing systems. Ensuring the high performance and the tunability of the system is essential to encode diverse functions. However, common strategies, including the integration of external electrode arrays or photonic structures with 2D materials, and barely patterned 2D materials, exhibit a contradiction between performance and tunability. Because the unique band dispersions of 2D materials can provide hidden paths to boost nonlinear responses independently, here we introduced a new free-space optical computing concept within a bare molybdenum disulfide array. This system can preserve high modulation performance with fast speed, low energy consumption, and high signal-to-noise ratio. Due to the freedom from the restrictions of fixed photonic structures, the tunability is also enhanced through the synergistic encodings of the 2D cells and the excitation pulses. The computing mechanism of transition from two-photon absorption to synergistic excited states absorption intrinsically improved the modulation capability of nonlinear optical responses, revealed from the relative transmittance modulated by a pump-probe-control strategy. Optical artificial neural network (ANN) and digital processing were demonstrated, revealing the feasibility of the free-space optical computing based on bare 2D materials toward neuromorphic applications.

Climate change is altering the thermal habitats of freshwater fish species. We analyze modeled daily temperature profiles from 12,688 lakes in the US to track changes in thermal habitat of 60 lake fish species from different thermal guilds during 1980-2021. We quantify changes in each species’ preferred days, defined as the number of days per year when a lake contains the species’ preferred temperature. We find that cooler-water species are losing preferred days more rapidly than warmer-water species are gaining them. This asymmetric impact cannot be attributed to differences in geographic distribution among species; instead, it is linked to the seasonal dynamics of lake temperatures and increased thermal homogenization of the water column. The potential advantages of an increase in warmer-water species may not fully compensate for the losses in cooler-water species as warming continues, emphasizing the importance of mitigating climate change to support effective freshwater fisheries management.