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MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis and have great potential for the diagnosis and treatment of cancer. However, the roles of miRNAs in hepatocellular carcinogenesis are still not fully elucidated. We investigated the aberrantly expressed miRNAs involved in hepatoma by comparison of miRNA expression profiles in cancerous hepatocytes with normal primary human hepatocytes, and 37 dysregulated miRNAs were screened out by twofold change with a significant difference ( P <0.05). Clustering analysis based on 13 miRNAs with changes over 15-folds showed that the miRNA expression patterns between the cancerous and normal hepatocytes were clearly different. Among the 13 miRNAs, we found that miR-375 was significantly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. Overexpression of miR-375 in liver cancer cells decreased cell proliferation, clonogenicity, migration/invasion and also induced G1 arrest and apoptosis. To unveil the molecular mechanism of miR-375-mediated phenotype in hepatoma cells described above, we examined the putative targets using bioinformatics tools and found that astrocyte elevated gene-1 (AEG-1) was a potential target of miR-375. Then we demonstrated that miR-375 bound directly to the 3′-untranslated region of AEG-1 and inhibited the expression of AEG-1. TaqMan quantitative reverse transcriptase–PCR and western blot analysis showed that miR-375 expression was inversely correlated with AEG-1 expression in HCC tissues. Knockdown of AEG-1 by RNAi in HCC cells, similar to miR-375 overexpression, suppressed tumor properties. Ectopic expression of AEG-1, conversely, could partially reverse the antitumor effects of miR-375. In a mouse model, therapeutic administration of cholesterol-conjugated 2′- O -methyl-modified miR-375 mimics (Chol-miR-375) could significantly suppress the growth of hepatoma xenografts in nude mice. In conclusion, our findings indicate that miR-375 targets AEG-1 in HCC and suppresses liver cancer cell growth in vitro and in vivo , and highlight the therapeutic potential of miR-375 in HCC treatment.

Cuprate superconductors have many unusual properties even in the “normal” (nonsuperconducting) regions of their phase diagram. In the so-called “strange metal” phase, these materials have resistivity that scales linearly with temperature, in contrast to the usual quadratic dependence of ordinary metals. Giraldo-Gallo et al. now find that at very high magnetic fields—up to 80 tesla—the resistivity of the thin films of a lanthanum-based cuprate scales linearly with magnetic field as well, again in contrast to the expected quadratic law. This dual linear dependence presents a challenge for theories of the normal state of the cuprates. Science , this issue p. 479 At high magnetic fields up to 80 tesla, the resistivity of a thin-film La-based cuprate scales linearly with the field. The anomalous metallic state in the high-temperature superconducting cuprates is masked by superconductivity near a quantum critical point. Applying high magnetic fields to suppress superconductivity has enabled detailed studies of the normal state, yet the direct effect of strong magnetic fields on the metallic state is poorly understood. We report the high-field magnetoresistance of thin-film La 2– x Sr x CuO 4 cuprate in the vicinity of the critical doping, 0.161 ≤ p ≤ 0.190. We find that the metallic state exposed by suppressing superconductivity is characterized by magnetoresistance that is linear in magnetic fields up to 80 tesla. The magnitude of the linear-in-field resistivity mirrors the magnitude and doping evolution of the well-known linear-in-temperature resistivity that has been associated with quantum criticality in high-temperature superconductors.

The scaling law for the critical temperature and zero-temperature stiffness in an overdoped copper oxide semiconductor does not conform to the standard Bardeen–Cooper–Schrieffer description. The physics of La 2−x Sr x CuO 4 superconductivity Ivan Božović et al . present a comprehensive study of the key physical properties of the overdoped copper oxide superconductor La 2−x Sr x CuO 4 . Their results run counter to the common assumption that strongly correlated fermion physics evolves smoothly into conventional Bardeen–Cooper–Schrieffer (BCS) behaviour in overdoped copper oxide superconductors. Rather, in La 2−x Sr x CuO 4 the scaling law for the critical superconducting temperature and zero-temperature phase stiffness does not conform to standard BCS physics. The authors speculate that the high critical temperature derives from local electron pairing and unusual kinematics. The physics of underdoped copper oxide superconductors, including the pseudogap, spin and charge ordering and their relation to superconductivity 1 , 2 , 3 , is intensely debated. The overdoped copper oxides are perceived as simpler, with strongly correlated fermion physics evolving smoothly into the conventional Bardeen–Cooper–Schrieffer behaviour. Pioneering studies on a few overdoped samples 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 indicated that the superfluid density was much lower than expected, but this was attributed to pair-breaking, disorder and phase separation. Here we report the way in which the magnetic penetration depth and the phase stiffness depend on temperature and doping by investigating the entire overdoped side of the La 2− x Sr x CuO 4 phase diagram. We measured the absolute values of the magnetic penetration depth and the phase stiffness to an accuracy of one per cent in thousands of samples; the large statistics reveal clear trends and intrinsic properties. The films are homogeneous; variations in the critical superconducting temperature within a film are very small (less than one kelvin). At every level of doping the phase stiffness decreases linearly with temperature. The dependence of the zero-temperature phase stiffness on the critical superconducting temperature is generally linear, but with an offset; however, close to the origin this dependence becomes parabolic. This scaling law is incompatible with the standard Bardeen–Cooper–Schrieffer description.

The purpose of this study was to define the roles of miR-181a in determining sensitivity of cervical cancer to radiation therapy, to explore the underlying mechanism and to evaluate the potential of miR-181a as a biomarker for predicting radio-sensitivity. Tumor specimens from 18 patients with a histological diagnosis of squamous cervical carcinoma (stage IIIB) were used in the micro-RNA profiling and comparison. These patients never received any chemotherapy before radiation therapy. Human cervical cancer cell lines, SiHa and Me180, were used in vitro (cell culture) and in vivo (animal) studies. Transfection of tumor cells with the mimic or inhibitor of miR-181a , and reporter gene assay, were performed to investigate the role of miR-181a in determining radio-sensitivity and the target gene. Higher expression of miR-181a was observed in human cervical cancer specimens and cell lines that were insensitive to radiation therapy, as compared with sensitive cancer specimens and the cell lines. We also found that miR-181a negatively regulated the expression of PRKCD, a pro-apoptotic protein kinase, via targeting its 3′-untranslated region (UTR), thereby inhibiting irradiation-induced apoptosis and decreasing G 2 /M block. The role of miR-181a in conferring cellular resistance to radiation treatment was validated both in cell culture models and in mouse tumor xenograft models. The effect of miR-181a on radio-resistance was mediated through targeting the 3′-UTR of PRKCD gene. Thus, the expression level of miR-181a in cervical cancer may serve as a biomarker for sensitivity to radiation therapy, and targeting miR-181a may represent a new approach to sensitizing cervical cancer to radiation treatment.

Multiple myeloma (MM) is an incurable hematological malignancy. Chimeric antigen receptor (CAR)-expressing T cells have been demonstrated successfully in the clinic to treat B-lymphoid malignancies. However, the potential utility of antigen-specific CAR-engineered natural-killer (NK) cells to treat MM has not been explored. In this study, we determined whether CS1, a surface protein that is highly expressed on MM cells, can be targeted by CAR NK cells to treat MM. We successfully generated a viral construct of a CS1-specific CAR and expressed it in human NK cells. In vitro , CS1-CAR NK cells displayed enhanced MM cytolysis and interferon-γ (IFN-γ) production, and showed a specific CS1-dependent recognition of MM cells. Ex vivo , CS1-CAR NK cells also showed similarly enhanced activities when responding to primary MM tumor cells. More importantly, in an aggressive orthotopic MM xenograft mouse model, adoptive transfer of NK-92 cells expressing CS1-CAR efficiently suppressed the growth of human IM9 MM cells and also significantly prolonged mouse survival. Thus, CS1 represents a viable target for CAR-expressing immune cells, and autologous or allogeneic transplantation of CS1-specific CAR NK cells may be a promising strategy to treat MM.

The electronic nematic phase in copper oxide superconductors is found over a broad range of temperature and doping but is not aligned with the crystal axes. A new phase of copper oxides Despite decades of study, high-temperature superconducting copper oxides can still throw up surprises. Several studies have pointed to the existence of an enigmatic anisotropic electronic state — an 'electronic nematic' phase — lurking in regions of the phase diagram. This implies that the 'normal' state of these materials, at temperatures above the superconducting transition temperature, is markedly different from that of a normal metal. Jie Wu and colleagues bring these peculiarities into sharp focus by showing that this nematic phase is widespread, as they detect it at every doping level up to room temperature, and that, even more surprisingly, it is unconnected to the crystal axes of the oxide planes in which it resides. The origin of high-temperature superconductivity in copper oxides and the nature of the ‘normal’ state above the critical temperature are widely debated 1 , 2 , 3 . In underdoped copper oxides, this normal state hosts a pseudogap and other anomalous features; and in the overdoped materials, the standard Bardeen–Cooper–Schrieffer description fails 4 , challenging the idea that the normal state is a simple Fermi liquid. To investigate these questions, we have studied the behaviour of single-crystal La 2– x Sr x CuO 4 films through which an electrical current is being passed. Here we report that a spontaneous voltage develops across the sample, transverse (orthogonal) to the electrical current. The dependence of this voltage on probe current, temperature, in-plane device orientation and doping shows that this behaviour is intrinsic, substantial, robust and present over a broad range of temperature and doping. If the current direction is rotated in-plane by an angle ϕ , the transverse voltage oscillates as sin(2 ϕ ), breaking the four-fold rotational symmetry of the crystal. The amplitude of the oscillations is strongly peaked near the critical temperature for superconductivity and decreases with increasing doping. We find that these phenomena are manifestations of unexpected in-plane anisotropy in the electronic transport. The films are very thin and epitaxially constrained to be tetragonal (that is, with four-fold symmetry), so one expects a constant resistivity and zero transverse voltage, for every ϕ . The origin of this anisotropy is purely electronic—the so-called electronic nematicity. Unusually, the nematic director is not aligned with the crystal axes, unless a substantial orthorhombic distortion is imposed. The fact that this anisotropy occurs in a material that exhibits high-temperature superconductivity may not be a coincidence.

Primary liver cancer, predominantly consisting of hepatocellular carcinoma (HCC), is one of the most common and aggressive human malignancies worldwide. MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression post-transcriptionally. Emerging evidence indicates that miRNAs are often deregulated in HCC, and that some specific miRNAs are associated with the clinicopathological features of HCC. Recent work demonstrates that miRNAs have essential roles in HCC progression and directly contribute to cell proliferation, avoidance of apoptotic cell death, and metastasis of HCC by targeting a large number of critical protein-coding genes. The discovery of the aberrantly expressed miRNAs and their corresponding targets has opened a novel avenue to investigate the molecular mechanism of HCC progression and to develop potential therapeutics against HCC. In this review, we summarise current knowledge about the roles and validated targets of miRNAs in liver cancer progression.

Schrödinger cat states, quantum superpositions of macroscopically distinct classical states, are an important resource for quantum communication, quantum metrology and quantum computation. Especially, cat states in a phase space protected against phase-flip errors can be used as a logical qubit. However, cat states, normally generated in three-dimensional cavities and/or strong multi-photon drives, are facing the challenges of scalability and controllability. Here, we present a strategy to generate and preserve cat states in a coplanar superconducting circuit by the fast modulation of Kerr nonlinearity. At the Kerr-free work point, our cat states are passively preserved due to the vanishing Kerr effect. We are able to prepare a 2-component cat state in our chip-based device with a fidelity reaching 89.1% under a 96 ns gate time. Our scheme shows an excellent route to constructing a chip-based bosonic quantum processor. Schrodinger’s cat states constitute an important resource for quantum information processing, but present challenges in terms of scalabilty and controllability. Here, the authors exploit fast Kerr nonlinearity modulation to generate and store cat states in superconducting circuits in a more scalable way.

Progress in quantum computing and quantum cryptography requires efficient, electrically triggered, single-photon sources at room temperature in the telecom wavelengths. It has been long known that semiconducting single-wall carbon nanotubes (SWCNTs) display strong excitonic binding and emit light over a broad range of wavelengths, but their use has been hampered by a low quantum yield and a high sensitivity to spectral diffusion and blinking. In this Perspective, we discuss recent advances in the mastering of SWCNT optical properties by chemistry, electrical contacting and resonator coupling towards advancing their use as quantum light sources. We describe the latest results in terms of single-photon purity, generation efficiency and indistinguishability. Finally, we consider the main fundamental challenges stemming from the unique properties of SWCNTs and the most promising roads for SWCNT-based chip integrated quantum photonic sources.

Lead halide perovskites exhibit structural instabilities and large atomic fluctuations thought to impact their optical and thermal properties, yet detailed structural and temporal correlations of their atomic motions remain poorly understood. Here, these correlations are resolved in CsPbBr 3 crystals using momentum-resolved neutron and X-ray scattering measurements as a function of temperature, complemented with first-principles simulations. We uncover a striking network of diffuse scattering rods, arising from the liquid-like damping of low-energy Br-dominated phonons, reproduced in our simulations of the anharmonic phonon self-energy. These overdamped modes cover a continuum of wave vectors along the edges of the cubic Brillouin zone, corresponding to two-dimensional sheets of correlated rotations in real space, and could represent precursors to proposed two-dimensional polarons. Further, these motions directly impact the electronic gap edge states, linking soft anharmonic lattice dynamics and optoelectronic properties. These results provide insights into the highly unusual atomic dynamics of halide perovskites, relevant to further optimization of their optical and thermal properties. Neutron and X-ray scattering measurements provide further insight into the anharmonic behaviour of lead halide perovskites, revealing that rotations of PbBr 6 octahedra in CsPbBr 3 crystals occur in a correlated fashion along two-dimensional planes.