Nature Communications最新文献

Deposition of misfolded α-synuclein (αsyn) in the enteric nervous system (ENS) is found in multiple neurodegenerative diseases. It is hypothesized that ENS synucleinopathy contributes to both the pathogenesis and non-motor morbidity in Parkinson's Disease (PD), but the cellular and molecular mechanisms that shape enteric histopathology and dysfunction are poorly understood. Here, we employ a fibrillar injection model of enteric synucleinopathy in male mice and demonstrate that ENS-resident macrophages, which play a critical role in maintaining ENS homeostasis, initially respond to enteric neuronal αsyn pathology by upregulating machinery for complement-mediated engulfment. Pharmacologic depletion of ENS-macrophages or genetic deletion of C1q enhanced enteric neuropathology. Conversely, C1q deletion ameliorated gut dysfunction, indicating that complement partially mediates αsyn-induced gut dysfunction. However, this C1q-dependent clearance mechanism diminished over time and its failure temporally correlated with the further increase in ENS pathology. These findings highlight the importance of enteric neuron-macrophage interactions in removing toxic protein aggregates that putatively shape the gastrointestinal manifestations of PD.

In semiconductor hole spin qubits, low magnetic field (B) operation extends the coherence time ( $T_2^{*}$ ) but proportionally reduces the gate speed. In contrast, singlet-triplet (ST) qubits are primarily controlled by the exchange interaction ( J) and can thus maintain high gate speeds even at low B. However, a large J introduces a significant charge component to the qubit, rendering ST qubits more vulnerable to charge noise when driven. Here, we demonstrate a highly coherent ST hole spin qubit in germanium, operating at both low B and low J. By modulating J, we achieve resonant driving of the ST qubit, obtaining an average gate fidelity of 99.68% and a coherence time of $T_2^{*}=1.9\mu s$ . Moreover, by applying the resonant drive continuously, we realize a dressed ST qubit with a tenfold increase in coherence time ( $T_{2\rho }^{*}=20.3\mu s$ ). Frequency modulation of the driving signal enables universal control, with an average gate fidelity of 99.63%. Our results demonstrate the potential for extending coherence times while preserving high-fidelity control of germanium-based ST qubits, paving the way for more efficient operations in semiconductor-based quantum processors.

Confined spaces are omnipresent in the micro-environments, including soil aggregates and intestinal crypts, yet little is known about how bacteria behave under such conditions where movement is challenging due to spatial confinement that limited effective diffusion. Stinkbug symbiont Caballeronia insecticola navigates a narrow gut passage about one micrometer in diameter to reach the stinkbug's symbiotic organ. Here, we developed a microfluidic device mimicking the host's sorting organ, wherein bacterial cells are confined in a quasi-one-dimensional fashion, and revealed that this bacterium wraps flagellar filaments around its cell body like a screw thread to control fluid flow and generate propulsion for smooth and directional movement in narrow passages. Physical simulations and genetic experiments revealed that hook flexibility is essential for this wrapping; increasing hook rigidity impaired both wrapping motility and infectivity. Thus, flagellar wrapping likely represents an evolutionary innovation, enabling bacteria to break through confined environments using their motility machinery.

MicroRNAs direct Argonaute proteins to repress complementary target mRNAs via mRNA degradation or translational inhibition. While mammalian miRNA targeting has been well studied, the principles by which Drosophila miRNAs bind their target RNAs remain to be fully characterized. Here, we use RNA Bind-n-Seq to systematically identify binding sites and measure their affinities for five highly expressed Drosophila miRNAs. Our results reveal a narrower range of binding site diversity in flies compared to mammals, with fly miRNAs favoring canonical seed-matched sites and exhibiting limited tolerance for imperfections within these sites. We also identified non-canonical site types, including nucleation-bulged and 3'-only sites, whose binding affinities are comparable to canonical sites. These findings establish a foundation for future computational models of Drosophila miRNA targeting, enabling predictions of regulatory outcomes in response to cellular signals, and advancing our understanding of miRNA-mediated regulation in flies.

Adoptive T cell therapy using chimeric antigen receptor (CAR) engineered T cells is currently being explored in multiple cancer types beyond leukemia/lymphoma. A key step in CAR-T cell manufacturing is the activation and expansion of T cells, which facilitates viral transduction, however, may hamper T cell fitness and reduce in vivo persistence. "T-Expand" is developed for T cell activation and expansion, comprising dextran-based nanoparticles conjugated with anti-CD3 and anti-CD28 antibodies. The nanoparticles trigger robust polyclonal expansion of human T cells with efficiency in the range of commercial microbeads (Dynabeads™). Engineered in the presence of T-Expand, CD19 CAR T cells display enhanced proliferative capacity, cytotoxicity and persistence in vitro, and furthermore, exhibit potent anti-lymphoma activity in mouse models, resulting in complete tumor clearance at one fourth of the CAR T cell dose. Importantly, T-Expand is biocompatible with no observed toxicity, circumventing removal steps after T cell expansion compared to Dynabeads^TM. As a biocompatible T cell expansion platform, T-Expand simplifies the manufacturing process while enhancing T cell persistence and functionality, and thereby holds promise for increasing clinical efficacy of CAR T cell therapy.

Quantum metrology has emerged as a powerful tool for timekeeping, field sensing, and precision measurements in fundamental physics. With the advent of distributed quantum metrology, its capabilities have extended to probing spatially distributed parameters across networked quantum systems. However, scalable implementations of distributed quantum metrology with multiparameter estimation remain limited, particularly due to the challenges of generating and distributing entanglement across a quantum network and dealing with incompatibilities in multiparameter quantum metrology. Here we demonstrate distributed multiparameter quantum metrology on a modular superconducting quantum network with low-loss microwave interconnects, a platform that uniquely combines fast gate operations, adaptive control, and deterministic non-local entanglement generation. Using a control-enhanced sequential protocol, we estimate all three components of a remote vector field, achieving up to 13.72 dB improvement in precision over the individual strategy. We further perform direct estimation of vector field gradients along two directions across spatially separated nodes, realizing a 3.44 dB gain over local entanglement strategies. These results establish superconducting quantum networks as a competitive and reconfigurable platform for scalable multiparameter distributed quantum metrology.