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The dispersive sweep of fast radio bursts (FRBs) has been used to probe the ionized baryon content of the intergalactic medium 1 , which is assumed to dominate the total extragalactic dispersion. Although the host-galaxy contributions to the dispersion measure appear to be small for most FRBs 2 , in at least one case there is evidence for an extreme magneto-ionic local environment 3 , 4 and a compact persistent radio source 5 . Here we report the detection and localization of the repeating FRB 20190520B, which is co-located with a compact, persistent radio source and associated with a dwarf host galaxy of high specific-star-formation rate at a redshift of 0.241 ± 0.001. The estimated host-galaxy dispersion measure of approximately 903 − 111 + 72 parsecs per cubic centimetre, which is nearly an order of magnitude higher than the average of FRB host galaxies 2 , 6 , far exceeds the dispersion-measure contribution of the intergalactic medium. Caution is thus warranted in inferring redshifts for FRBs without accurate host-galaxy identifications. A repeating fast radio burst co-located with a persistent radio source and associated with a dwarf host galaxy of a high star-formation rate has been detected.

Hypertrophic cardiomyopathy (HCM) is the most prominent cause of sudden cardiac death in young people. Due to heterogeneity in clinical manifestations, conventional HCM drugs have limitations for mitochondrial hypertrophic cardiomyopathy. Discovering more effective compounds would be of substantial benefit for further elucidating the pathogenic mechanisms of HCM and treating patients with this condition. We previously reported the MT-RNR2 variant associated with HCM that results in mitochondrial dysfunction. Here, we screened a mitochondria-associated compound library by quantifying the mitochondrial membrane potential of HCM cybrids and the survival rate of HCM-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) in galactose media. 1-Deoxynojirimycin (DNJ) was identified to rescue mitochondrial function by targeting optic atrophy protein 1 (OPA1) to promote its oligomerization, leading to reconstruction of the mitochondrial cristae. DNJ treatment further recovered the physiological properties of HCM iPSC-CMs by improving Ca2+ homeostasis and electrophysiological properties. An angiotensin II-induced cardiac hypertrophy mouse model further verified the efficacy of DNJ in promoting cardiac mitochondrial function and alleviating cardiac hypertrophy in vivo. These results demonstrated that DNJ could be a potential mitochondrial rescue agent for mitochondrial hypertrophic cardiomyopathy. Our findings will help elucidate the mechanism of HCM and provide a potential therapeutic strategy.

Magnetization plateaus in quantum magnets—where bosonic quasiparticles crystallize into emergent spin superlattices—are spectacular yet simple examples of collective quantum phenomena escaping classical description. While magnetization plateaus have been observed in a number of spin-1/2 antiferromagnets, the description of their magnetic excitations remains an open theoretical and experimental challenge. Here, we investigate the dynamical properties of the triangular-lattice spin-1/2 antiferromagnet Ba 3 CoSb 2 O 9 in its one-third magnetization plateau phase using a combination of nonlinear spin-wave theory and neutron scattering measurements. The agreement between our theoretical treatment and the experimental data demonstrates that magnons behave semiclassically in the plateau in spite of the purely quantum origin of the underlying magnetic structure. This allows for a quantitative determination of Ba 3 CoSb 2 O 9 exchange parameters. We discuss the implication of our results to the deviations from semiclassical behavior observed in zero-field spin dynamics of the same material and conclude they must have an intrinsic origin. Frustrated magnetic materials attract significant interest because their properties can become dominated by quantum fluctuations. Here the authors show that excitations in the plateau phase of a quantum magnet can be understood semiclassically even though the ground state involves strong quantum effects.

Indium-substituted strontium hexaferrites were prepared by the conventional solid-phase reaction method. Neutron diffraction patterns were obtained at room temperature and analyzed using the Rietveld methods. A linear dependence of the unit cell parameters is found. In 3+ cations are located mainly in octahedral positions of 4f VI and 12 k. The average crystallite size varies within 0.84–0.65 μm. With increasing substitution, the T C Curie temperature decreases monotonically down to ~ 520 K. ZFC and FC measurements showed a frustrated state. Upon substitution, the average and maximum sizes of ferrimagnetic clusters change in the opposite direction. The M r remanent magnetization decreases down to ~ 20.2 emu/g at room temperature. The M s spontaneous magnetization and the k eff effective magnetocrystalline anisotropy constant are determined. With increasing substitution, the maximum of the ε / real part of permittivity decreases in magnitude from ~ 3.3 to ~ 1.9 and shifts towards low frequencies from ~ 45.5 GHz to ~ 37.4 GHz. The maximum of the tg(α) dielectric loss tangent decreases from ~ 1.0 to ~ 0.7 and shifts towards low frequencies from ~ 40.6 GHz to ~ 37.3 GHz. The low-frequency maximum of the μ / real part of permeability decreases from ~ 1.8 to ~ 0.9 and slightly shifts towards high frequencies up to ~ 34.7 GHz. The maximum of the tg(δ) magnetic loss tangent decreases from ~ 0.7 to ~ 0.5 and shifts slightly towards low frequencies from ~ 40.5 GHz to ~ 37.7 GHz. The discussion of microwave properties is based on the saturation magnetization, natural ferromagnetic resonance and dielectric polarization types.

The amyloid-β protein (Aβ) protein plays a pivotal role in the pathogenesis of Alzheimer’s disease (AD). It is believed that Aβ deposited in the brain originates from the brain tissue itself. However, Aβ is generated in both brain and peripheral tissues. Whether circulating Aβ contributes to brain AD-type pathologies remains largely unknown. In this study, using a model of parabiosis between APPswe/PS1dE9 transgenic AD mice and their wild-type littermates, we observed that the human Aβ originated from transgenic AD model mice entered the circulation and accumulated in the brains of wild-type mice, and formed cerebral amyloid angiopathy and Aβ plaques after a 12-month period of parabiosis. AD-type pathologies related to the Aβ accumulation including tau hyperphosphorylation, neurodegeneration, neuroinflammation and microhemorrhage were found in the brains of the parabiotic wild-type mice. More importantly, hippocampal CA1 long-term potentiation was markedly impaired in parabiotic wild-type mice. To the best of our knowledge, our study is the first to reveal that blood-derived Aβ can enter the brain, form the Aβ-related pathologies and induce functional deficits of neurons. Our study provides novel insight into AD pathogenesis and provides evidence that supports the development of therapies for AD by targeting Aβ metabolism in both the brain and the periphery.

In Alzheimer’s disease (AD), neurodegenerative signals such as amyloid-beta (Aβ) and the precursors of neurotrophins, outbalance neurotrophic signals, causing synaptic dysfunction and neurodegeneration. The neurotrophin receptor p75 (p75NTR) is a receptor of Aβ and mediates Aβ-induced neurodegenerative signals. The shedding of its ectodomain from the cell surface is physiologically regulated; however, the function of the diffusible p75NTR ectodomain (p75ECD) after shedding remains largely not known. Here, we show that p75ECD levels in cerebrospinal fluid and in the brains of Alzheimer’s patients and amyloid-beta precursor protein (APP)/PS1 transgenic mice were significantly reduced, due to inhibition of the sheddase-tumor necrosis factor-alpha-converting enzyme by Aβ. Restoration of p75ECD to the normal level by brain delivery of the gene encoding human p75ECD before or after Aβ deposition in the brain of APP/PS1 mice reversed the behavioral deficits and AD-type pathologies, such as Aβ deposit, apoptotic events, neuroinflammation, Tau phosphorylation and loss of dendritic spine, neuronal structures and synaptic proteins. Furthermore, p75ECD can also reduce amyloidogenesis by suppressing β-secretase expression and activities. Our data demonstrate that p75ECD is a physiologically neuroprotective molecule against Aβ toxicity and would be a novel therapeutic target and biomarker for AD.

The most fascinating feature of certain two-dimensional (2D) gapless quantum spin liquid (QSL) is that their spinon excitations behave like the fermionic carriers of a paramagnetic metal. The spinon Fermi surface is then expected to produce a linear increase of the thermal conductivity with temperature that should manifest via a residual value ( κ 0 / T ) in the zero-temperature limit. However, this linear in T behavior has been reported for very few QSL candidates. Here, we studied the ultralow-temperature thermal conductivity of an effective spin-1/2 triangular QSL candidate Na 2 BaCo(PO 4 ) 2 , which has an antiferromagnetic order at very low temperature ( T N ~ 148 mK), and observed a finite κ 0 / T extrapolated from the data above T N . Moreover, while approaching zero temperature, it exhibits series of quantum spin state transitions with applied field along the c axis. These observations indicate that Na 2 BaCo(PO 4 ) 2 possibly behaves as a gapless QSL with itinerant spin excitations above T N and its strong quantum spin fluctuations persist below T N . Thermal conductivity evidence of a spinon Fermi surface has been rare. Here, the authors report a finite linear increase of thermal conductivity with temperature in Na 2 BaCo(PO 4 ) 2 at ultra-low temperature, suggesting possible gapless quantum spin liquid behavior.

Reduced expression of brain-derived neurotrophic factor (BDNF) has a crucial role in the pathogenesis of Alzheimer’s disease (AD), which is characterized with the formation of neuritic plaques consisting of amyloid-beta (Aβ) and neurofibrillary tangles composed of hyperphosphorylated tau protein. A growing body of evidence indicates a potential protective effect of BDNF against Aβ-induced neurotoxicity in AD mouse models. However, the direct therapeutic effect of BDNF supplement on tauopathy in AD remains to be established. Here, we found that the BDNF level was reduced in the serum and brain of AD patients and P301L transgenic mice (a mouse model of tauopathy). Intralateral ventricle injection of adeno-associated virus carrying the gene encoding human BDNF (AAV-BDNF) achieved stable expression of BDNF gene and restored the BDNF level in the brains of P301L mice. Restoration of the BDNF level attenuated behavioral deficits, prevented neuron loss, alleviated synaptic degeneration and reduced neuronal abnormality, but did not affect tau hyperphosphorylation level in the brains of P301L mice. Long-term expression of AAV-BDNF in the brain was well tolerated by the mice. These findings suggest that the gene delivery of BDNF is a promising treatment for tau-related neurodegeneration for AD and other neurodegenerative disorders with tauopathy.

The microRNA-371-373 (miR-371-373) cluster is specifically expressed in human embryonic stem cells (ESCs) and is thought to be involved in stem cell maintenance. Recently, microRNAs (miRNAs) of this cluster were shown to be frequently upregulated in several human tumors. However, the regulatory mechanism for the involvement of the miR-371-373 cluster in human ESCs or cancer cells remains unclear. In this study, we explored the relationship between this miRNA cluster and the Wnt/β-catenin-signaling pathway, which has been shown to be involved in both stem cell maintenance and tumorigenesis. We show that miR-371-373 expression is induced by lithium chloride and is positively correlated with Wnt/β-catenin-signaling activity in several human cancer cell lines. Mechanistically, three TCF/LEF1-binding elements (TBEs) were identified in the promoter region and shown to be required for Wnt-dependent activation of miR-371-373. Interestingly, we also found that miR-372&373, in turn, activate Wnt/β-catenin signaling. In addition, four protein genes related to the Wnt/β-catenin-signaling pathway were identified as direct targets of miR-372&373, including Dickkopf-1 ( DKK1 ), a well-known inhibitor of Wnt/β-catenin signaling. Using a lentiviral system, we showed that overexpression of miR-372 or miR-373 promotes cell growth and the invasive activity of tumor cells as knockdown of DKK1. Taken together, our study demonstrates a novel β-catenin/LEF1–miR-372&373–DKK1 regulatory feedback loop, which may have a critical role in regulating the activity of Wnt/β-catenin signaling in human cancer cells.

With their high storage capacity and energy efficiency as well as the compatibilities with renewable energy sources, high‐temperature aquifer thermal energy storage (HT‐ATES) systems are frequently the target today in the design of temporally and spatially balanced and continuous energy supply systems. The inherent density‐driven buoyancy flow is of greater importance with HT‐ATES, which may lead to a lower thermal recovery efficiency than conventional low‐temperature ATES. In this study, the governing equations for HT‐ATES considering buoyancy flow are nondimensionalized, and four key dimensionless parameters regarding thermal recovery efficiency are determined. Then, using numerical simulations, recovery efficiency for a sweep of the key dimensionless parameters for multiple cycles and storage volumes is examined. Ranges of the key dimensionless parameters for the three displacement regimes, that is, a buoyancy‐dominated regime, a conduction‐dominated regime, and a transition regime, are identified. In the buoyancy‐dominated regime, recovery efficiency is mainly correlated to the ratio between the Rayleigh number and the Peclet number. In the conduction‐dominated regime, recovery efficiency is mainly correlated to the product of a material‐related parameter and the Peclet number. Multivariable regression functions are provided to estimate recovery efficiency using the dimensionless parameters. The recovery efficiency estimated by the regression function shows good agreement with the simulation results. Additionally, well screen designs for optimizing recovery efficiency at various degrees of intensity of buoyancy flow are investigated. The findings of this study can be used for a quick assessment and characterization of the potential HT‐ATES systems based on the geological and operational parameters. Key Points Four key dimensionless parameters for the high‐temperature aquifer thermal energy storage systems are identified The displacement processes are classified into a buoyancy‐dominated regime, a conduction‐dominated regime, and a transition regime Multivariable regression functions are demonstrated for the estimation of thermal recovery efficiency