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The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 10 15 electronvolts) indicates the existence of the so-called PeVatrons—cosmic-ray factories that accelerate particles to PeV energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays 1 . The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref. 2 ). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane 3 – 6 , unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators. Observations of γ-rays with energies up to 1.4 PeV find that 12 sources in the Galaxy are PeVatrons, one of which is the Crab Nebula.

Accumulating evidence suggests that microRNAs (miRNAs) are important gene regulators, which can have critical roles in diverse biological processes including tumorigenesis. In this study, we analyzed the miRNA expression profiles in non-small cell lung carcinoma (NSCLC) by use of a miRNA microarray platform and identified 40 differentially expressed miRNAs. We showed that miRNA (miR)-451 was the most downregulated in NSCLC tissues. The expression level of miR-451 was found to be significantly correlated with tumor differentiation, pathological stage and lymph-node metastasis. Moreover, low miR-451 expression level was also correlated with shorter overall survival of NSCLC patients ( P <0.001). Ectopic miR-451 expression significantly suppressed the in vitro proliferation and colony formation of NSCLC cells and the development of tumors in nude mice by enhancing apoptosis, which might be associated with inactivation of Akt signaling pathway. Interestingly, ectopic miR-451 expression could significantly inhibit RAB14 protein expression and decrease a luciferase-reporter activity containing the RAB14 3′-untranslated region (UTR). In addition,, RNA interference silencing of RAB14 gene could recapitulate the tumor suppressor function of miR-451, whereas restoration of RAB14 expression could partially attenuate the tumor suppressor function of miR-451 in NSCLC cells. Furthermore, we also showed that strong positive immunoreactivity of RAB14 protein was significantly associated with downregulation of miR-451 ( P =0.01). These findings suggest that miR-451 regulates survival of NSCLC cells partially through the downregulation of RAB14. Therefore, targeting with the miR-451/RAB14 interaction might serve as a novel therapeutic application to treat NSCLC patients.

As a quantum material, Weyl semimetal has a series of electronic-band-structure features, including Weyl points with left and right chirality and corresponding Berry curvature, which have been observed in experiments. These band-structure features also lead to some unique nonlinear properties, especially high-order harmonic generation (HHG) due to the dynamic process of electrons under strong laser excitation, which has remained unexplored previously. Herein, we obtain effective HHG in type-II Weyl semimetal β-WP 2 crystals, where both odd and even orders are observed, with spectra extending into the vacuum ultraviolet region (190 nm, 10th order), even under fairly low femtosecond laser intensity. In-depth studies have interpreted that odd-order harmonics come from the Bloch electron oscillation, while even orders are attributed to Bloch oscillations under the “spike-like” Berry curvature at Weyl points. With crystallographic orientation-dependent HHG spectra, we further quantitatively retrieved the electronic band structure and Berry curvature of β-WP 2 . These findings may open the door for exploiting metallic/semimetallic states as solid platforms for deep ultraviolet radiation and offer an all-optical and pragmatic solution to characterize the complicated multiband electronic structure and Berry curvature of quantum topological materials. Weyl semimetals have interesting band-structure features that lead to unique properties. Here, the authors observe and study high-harmonic generation in type-II Weyl semimetal β-WP2 crystals.

Topological valley states at the domain wall between two artificial crystals with opposite valley Chern numbers offer a feasible way to realize robust wave transport since only broken spatial symmetry is required. In addition to the valley, spin and crystal dimension are two other important degrees of freedom, particularly in realizing spin-related topological phenomena. Here we experimentally demonstrate that it is possible to construct two-dimensional acoustic topological pseudospin-valley coupled saddle surface states, designed from glide symmetry in a three-dimensional system. By taking advantage of such two-dimensional surface states, a full set of acoustic pseudospins can be realized, exhibiting pseudospin-valley dependent transport. Furthermore, due to the hyperbolic character of the dispersion of saddle surface states, multi-directional anisotropic controllable robust sound transport with little backscattering is observed. Our findings may open research frontiers for acoustic pseudospins and provide a satisfactory platform for exploring unique acoustic topological properties in three-dimensional structures. Valley states can be used to realise topologically protected transport. Here, He et al. show that considering additional degrees of freedom, together with glide symmetry, allow the design of 2D acoustic topological pseudospin-valley coupled saddle surface states in 3D structures.

A viscous damping model is proposed based on a simplified equation of fluid motion in a moonpool or the narrow gap formed by two fixed boxes. The model takes into account the damping induced by both flow separation and wall friction through two damping coefficients, namely, the local and friction loss coefficients. The local loss coefficient is determined through specifically designed physical model tests in this work, and the friction loss coefficient is estimated through an empirical formula found in the literature. The viscous damping model is implemented in the dynamic free-surface boundary condition in the gap of a modified potential flow model. The modified potential flow model is then applied to simulate the wave-induced fluid responses in a narrow gap formed by two fixed boxes and in a moonpool for which experimental data are available. The modified potential flow model with the proposed viscous damping model works well in capturing both the resonant amplitude and frequency under a wide range of damping conditions.

Commercial lead-based piezoelectric materials raised worldwide environmental concerns in the past decade. Bi 0.5 Na 0.5 TiO 3 -based solid solution is among the most promising lead-free piezoelectric candidates; however, depolarization of these solid solutions is a longstanding obstacle for their practical applications. Here we use a strategy to defer the thermal depolarization, even render depolarization-free Bi 0.5 Na 0.5 TiO 3 -based 0–3-type composites. This is achieved by introducing semiconducting ZnO particles into the relaxor ferroelectric 0.94Bi 0.5 Na 0.5 TiO 3 –0.06BaTiO 3 matrix. The depolarization temperature increases with increasing ZnO concentration until depolarization disappears at 30 mol% ZnO. The semiconducting nature of ZnO provides charges to partially compensate the ferroelectric depolarization field. These results not only pave the way for applications of Bi 0.5 Na 0.5 TiO 3 -based piezoceramics, but also have great impact on the understanding of the mechanism of depolarization so as to provide a new design to optimize the performance of lead-free piezoelectrics. Piezoelectric materials are used as sensors or actuators in many devices. Here, the authors demonstrate that semiconducting ZnO particles embedded into a Bi 0.5 Na 0.5 TiO 3 -based matrix improve its piezoelectric properties, promising an alternative to presently used lead-based materials.

New data show that R loops differentially modulate binding of chromatin remodelers Tip60–p400 and PRC2 at coding and noncoding gene promoters of mouse ESCs and thereby control transcription and cellular differentiation. Numerous chromatin-remodeling factors are regulated by interactions with RNA, although the contexts and functions of RNA binding are poorly understood. Here we show that R loops, RNA-DNA hybrids consisting of nascent transcripts hybridized to template DNA, modulate the binding of two key chromatin-regulatory complexes, Tip60–p400 and polycomb repressive complex 2 (PRC2) in mouse embryonic stem cells (ESCs). Like PRC2, the Tip60–p400 histone acetyltransferase complex binds to nascent transcripts; however, transcription promotes chromatin binding of Tip60–p400 but not PRC2. Interestingly, we observed higher Tip60–p400 and lower PRC2 levels at genes marked by promoter-proximal R loops. Furthermore, disruption of R loops broadly decreased Tip60–p400 occupancy and increased PRC2 occupancy genome wide. In agreement with these alterations, ESCs partially depleted of R loops exhibited impaired differentiation. These results show that R loops act both positively and negatively in modulating the recruitment of key pluripotency regulators.

Background The association of advanced digital image correlation (DIC) and numerical simulation has been widely used for inverse parameter identification. Objective It is attractive to develop an accurate DIC method sharing the common features with numerical simulation, which can lead to better synergy between experiments and simulations. Methods A new meshfree digital image correlation (MF-DIC) using element free Galerkin method (EFGM) is proposed for deformation measurement. The EFGM is a classical meshfree method in numerical studies, and it is directly used to construct the shape function in MF-DIC from a set of scattered nodes for image matching. The MF-DIC is principally different from the classical local DIC and global DIC since it does not rely on the concept of a subset or an element. Results In MF-DIC, the C 1 -continuous displacement for every point is constructed based on a group of scattered nodes in a small support domain surrounding it. The continuous strain map can then be directly derived from the displacement, instead of using an additional smoothing technique as required in classical local DIC or post-processing used in global DIC. A performance assessment based on the Metrological Efficiency Indicator (MEI), as defined in DIC Challenge 2.0, shows that the proposed MF-DIC yields an excellent balance between spatial resolution and measurement resolution for both displacement and strain measurements. Conclusions Given that the proposed MF-DIC shares common features with the classical meshfree method in computational mechanics, it paves the way for an enhanced synergy between experiments and simulations required for robust inverse parameter identification methods.

By directly altering microscopic interactions, pressure provides a powerful tuning knob for the exploration of condensed phases and geophysical phenomena 1 . The megabar regime represents an interesting frontier, in which recent discoveries include high-temperature superconductors, as well as structural and valence phase transitions 2 – 6 . However, at such high pressures, many conventional measurement techniques fail. Here we demonstrate the ability to perform local magnetometry inside a diamond anvil cell with sub-micron spatial resolution at megabar pressures. Our approach uses a shallow layer of nitrogen-vacancy colour centres implanted directly within the anvil 7 – 9 ; crucially, we choose a crystal cut compatible with the intrinsic symmetries of the nitrogen-vacancy centre to enable functionality at megabar pressures. We apply our technique to characterize a recently discovered hydride superconductor, CeH 9 (ref.  10 ). By performing simultaneous magnetometry and electrical transport measurements, we observe the dual signatures of superconductivity: diamagnetism characteristic of the Meissner effect and a sharp drop of the resistance to near zero. By locally mapping both the diamagnetic response and flux trapping, we directly image the geometry of superconducting regions, showing marked inhomogeneities at the micron scale. Our work brings quantum sensing to the megabar frontier and enables the closed-loop optimization of superhydride materials synthesis. In order to explore superconductivity in hydride materials, local magnetometry inside a diamond anvil cell is performed with sub-micron spatial resolution at megabar pressures using nitrogen-vacancy colour centres.

Considerable evidences have shown that autophagy has an important role in tumor chemoresistance. However, it is still unknown whether the lncRNA HULC (highly upregulated in liver cancer) is involved in autophagy and chemoresistance of hepatocellular carcinoma (HCC). In this study, we for the first time demonstrated that treatment with antitumor reagents such as oxaliplatin, 5-fluorouracil and pirarubicin (THP) dramatically induced HULC expression and protective autophagy. Silencing of HULC sensitized HCC cells to the three antitumor reagents via inhibiting protective autophagy. Ectopic expression of HULC elicited the autophagy of HCC cells through stabilizing silent information regulator 1 (Sirt1) protein. The investigation for the corresponding mechanism by which HULC stabilized Sirt1 revealed that HULC upregulated ubiquitin-specific peptidase 22 (USP22), leading to the decrease of ubiquitin-mediated degradation of Sirt1 protein by removing the conjugated polyubiquitin chains from Sirt1. Moreover, we found that miR-6825-5p, miR-6845-5p and miR-6886-3p could decrease the level of USP22 protein by binding to the 3′-untranlated region of USP22 mRNA. All the three microRNAs (miRNAs) were downregulated by HULC, which resulted in the elevation of USP22. In addition, we showed that the level of HULC was positively correlated with that of Sirt1 protein in human HCC tissues. Collectively, our data reveals that the pathway ‘HULC/USP22/Sirt1/ protective autophagy’ attenuates the sensitivity of HCC cells to chemotherapeutic agents, suggesting that this pathway may be a novel target for developing sensitizing strategy to HCC chemotherapy.