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Polystyrene nanoplastics potentiate the development of hepatic fibrosis throughout fatty diet provided rodents.
Phase boundary provides a fertile ground for exploring emergent phenomena and understanding order parameters couplings in condensed-matter physics. In Pb(Zr1-xTix)O3, there are two types of composition-dependent phase boundary with both technological and scientific importance, i.e. morphotropic phase boundary (MPB) separating polar regimes into different symmetry and ferroelectric/antiferroelectric (FE/AFE) phase boundary dividing polar and antipolar dipole configurations. In contrast with extensive studies on MPB, FE/AFE phase boundary is far less explored. Here, we apply atomic-scale imaging and Rietveld refinement to directly demonstrate the intermediate phase at FE/AFE phase boundary exhibits a rare multipolar Pb-cations ordering, i.e. coexistence of antipolar or polar displacement, which manifests itself in both periodically gradient lattice spacing and anomalous initial hysteresis loop. In-situ electron/neutron diffraction reveals that the same parent intermediate phase can transform into either FE or AFE state depending on suppression of antipolar or polar displacement, coupling with the evolution of long-/short-range oxygen octahedra tilts. First-principle calculations further show that the transition between AFE and FE phase can occur in a low-energy pathway via the intermediate phase. These findings enrich the structural understanding of FE/AFE phase boundary in perovskite oxides.Chromosomal inversions frequently underlie major phenotypic variation maintained by divergent selection within and between sexes. Here we examine whether and how intralocus conflicts contribute to balancing selection stabilizing an autosomal inversion polymorphism in the ruff Calidris pugnax. In this lekking shorebird, three male mating morphs (Independents, Satellites and Faeders) are controlled by an inversion-based supergene. We show that in a captive population, Faeder females, who are smaller and whose inversion haplotype has not undergone recombination, have lower average reproductive success in terms of laying rate, egg size, and offspring survival than Independent females, who lack the inversion. Satellite females, who carry a recombined inversion haplotype and have intermediate body size, more closely resemble Independent than Faeder females in reproductive performance. We inferred that the lower reproductive output of Faeder females is most likely balanced by higher than average reproductive success of individual Faeder males. These findings suggest that intralocus conflicts may play a major role in the evolution and maintenance of supergene variants.Photonic generation of Terahertz (THz) carriers displays high potential for THz communications with a large tunable range and high modulation bandwidth. While many photonics-based THz generations have recently been demonstrated with discrete bulky components, their practical applications are significantly hindered by the large footprint and high energy consumption. Herein, we present an injection-locked heterodyne source based on generic foundry-fabricated photonic integrated circuits (PIC) attached to a uni-traveling carrier photodiode generating high-purity THz carriers. The generated THz carrier is tunable within the range of 0-1.4 THz, determined by the wavelength spacing between the two monolithically integrated distributed feedback (DFB) lasers. This scheme generates and transmits a 131 Gbits-1 net rate signal over a 10.7-m distance with -24 dBm emitted power at 0.4 THz. This monolithic dual-DFB PIC-based THz generation approach is a significant step towards fully integrated, cost-effective, and energy-efficient THz transmitters.Molecular necklaces have attracted much research attention due to their unique topological structures. Although numerous molecular necklaces with exquisite structures have been constructed, it remains a major challenge to exploit the functions and applications associated with their fascinating architectural and dynamic characteristics. Herein, we report a class of mechanically interlocked networks (MINs) cross-linked by a molecular necklace, in which multiple crown ethers are threaded on a hexagonal metallacyclic framework to furnish a cross-linker with delicate interlocked structures. The molecular necklace cross-linker possesses multiple peculiar advantages multivalent interactions and rigid metallacycle framework guarantee robust features of MINs while the motion and dissociation of the interlocked structures bring in notable mechanical adaptivity. Moreover, the MINs could respond to the stimuli of K+ and Br-, which lead to the dethreading of crown ether and even the complete decomposition of molecular necklace, respectively, showing abundant active properties. These findings demonstrate the untapped potential of molecular necklaces as cross-linkers and open the door to extend their advanced applications in intelligent supramolecular materials.B-cells play a key role in cancer suppression, particularly when aggregated in tertiary lymphoid structures (TLS). Here, we investigate the role of B-cells and TLS in endometrial cancer (EC). Single cell RNA-sequencing of B-cells shows presence of naïve B-cells, cycling/germinal center B-cells and antibody-secreting cells. Differential gene expression analysis shows association of TLS with L1CAM overexpression. Immunohistochemistry and co-immunofluorescence show L1CAM expression in mature TLS, independent of L1CAM expression in the tumor. Using L1CAM as a marker, 378 of the 411 molecularly classified ECs from the PORTEC-3 biobank are evaluated, TLS are found in 19%. L1CAM expressing TLS are most common in mismatch-repair deficient (29/127, 23%) and polymerase-epsilon mutant EC (24/47, 51%). Multivariable Cox regression analysis shows strong favorable prognostic impact of TLS, independent of clinicopathological and molecular factors. RU58841 research buy Our data suggests a pivotal role of TLS in outcome of EC patients, and establishes L1CAM as a simple biomarker.Cellular plasticity contributes to intra-tumoral heterogeneity and phenotype switching, which enable adaptation to metastatic microenvironments and resistance to therapies. Mechanisms underlying tumor cell plasticity remain poorly understood. SOX10, a neural crest lineage transcription factor, is heterogeneously expressed in melanomas. Loss of SOX10 reduces proliferation, leads to invasive properties, including the expression of mesenchymal genes and extracellular matrix, and promotes tolerance to BRAF and/or MEK inhibitors. We identify the class of cellular inhibitor of apoptosis protein-1/2 (cIAP1/2) inhibitors as inducing cell death selectively in SOX10-deficient cells. Targeted therapy selects for SOX10 knockout cells underscoring their drug tolerant properties. Combining cIAP1/2 inhibitor with BRAF/MEK inhibitors delays the onset of acquired resistance in melanomas in vivo. These data suggest that SOX10 mediates phenotypic switching in cutaneous melanoma to produce a targeted inhibitor tolerant state that is likely a prelude to the acquisition of resistance. Furthermore, we provide a therapeutic strategy to selectively eliminate SOX10-deficient cells.Urban settlements are rapidly growing outward and upward, with consequences for resource use, greenhouse gas emissions, and ecosystem and public health, but rates of change are uneven around the world. Understanding trajectories and predicting consequences of global urban expansion requires quantifying rates of change with consistent, well-calibrated data. Microwave backscatter data provides important information on upward urban growth - essentially the vertical built-up area. We developed a multi-sensor, multi-decadal, gridded (0.05° lat/lon) data set of global urban microwave backscatter, 1993-2020. Comparison of backscatter from two C-band sensors (ERS and ASCAT) and one Ku-band sensor (QuikSCAT) are made at four invariant non-urban sites (~3500 km2) to evaluate instrument stability and multi-decadal pattern. For urban areas, there was a strong linear correlation (overall R2 = 0.69) between 2015 ASCAT urban backscatter and a continental-scale gridded product of building volume, across 8450 urban grid cells (0.05° × 0.05°) in Europe, China, and the USA. This urban backscatter data set provides a time series characterizing global urban change over the past three decades.Orbital-free density functional theory (OF-DFT) is an electronic structure method with a low computational cost that scales linearly with the number of simulated atoms, making it suitable for large-scale material simulations. It is generally considered that OF-DFT strictly requires the use of local pseudopotentials, rather than orbital-dependent nonlocal pseudopotentials, for the calculation of electron-ion interaction energies, as no orbitals are available. This is unfortunate situation since the nonlocal pseudopotentials are known to give much better transferability and calculation accuracy than local ones. We report here the development of a theoretical scheme that allows the direct use of nonlocal pseudopotentials in OF-DFT. In this scheme, a nonlocal pseudopotential energy density functional is derived by the projection of nonlocal pseudopotential onto the non-interacting density matrix (instead of "orbitals") that can be approximated explicitly as a functional of electron density. Our development defies the belief that nonlocal pseudopotentials are not applicable to OF-DFT, leading to the creation for an alternate theoretical framework of OF-DFT that works superior to the traditional approach.Cortical neural circuits are complex but very precise networks of balanced excitation and inhibition. Yet, the molecular and cellular mechanisms that form the balance are just beginning to emerge. Here, using conditional γ-aminobutyric acid receptor B1- deficient mice we identify a γ-aminobutyric acid/tumor necrosis factor superfamily member 12-mediated bidirectional communication pathway between parvalbumin-positive fast spiking interneurons and oligodendrocyte precursor cells that determines the density and function of interneurons in the developing medial prefrontal cortex. Interruption of the GABAergic signaling to oligodendrocyte precursor cells results in reduced myelination and hypoactivity of interneurons, strong changes of cortical network activities and impaired social cognitive behavior. In conclusion, glial transmitter receptors are pivotal elements in finetuning distinct brain functions.Polymer-based piezoelectric devices are promising for developing future wearable force sensors, nanogenerators, and implantable electronics, etc. The electric signals generated by them are often assumed as solely coming from the piezoelectric effect. However, triboelectric signals originated from contact electrification between the piezoelectric devices and the contacted objects can produce non-negligible interfacial electron transfer, which is often combined with the piezoelectric signal to give a triboelectric-piezoelectric hybrid output, leading to an exaggerated measured "piezoelectric" signal. Herein, a simple and effective method is proposed for quantitatively identifying and extracting the piezoelectric charge from the hybrid signal. The triboelectric and piezoelectric parts in the hybrid signal generated by a poly(vinylidene fluoride)-based device are clearly differentiated, and their force and charge characteristics in the time domain are identified. This work presents an effective method to elucidate the true piezoelectric performance in practical measurement, which is crucial for evaluating piezoelectric materials fairly and correctly.
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