A novel fast electron beam emitting along the surface of a target irradiated by intense laser pulses is observed. The beam is found to appear only when the plasma density scale length is small. Numerical simulations reveal that the electron beam is formed due to the confinement of the surface quasistatic electromagnetic fields. The results are of interest for potential applications of fast electron beams and deep understanding of the cone-target physics in the fast ignition related experiments.

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For cancer cells to proliferate, a balance must be built between biomass-forming, glucose-metabolized intermediates and ATP production. How intrinsic glucose carbon flow regulates this balance remains unclear. Here we show that mitochondrial phosphoenolpyruvate carboxykinase (PCK2), the hub molecule linking tricarboxylic acid (TCA) cycle, glycolysis and gluconeogenesis by conversion of mitochondrial oxaloacetate (OAA) to phosphoenolpyruvate, regulates glucose carbon flow direction in stem-like cells that repopulate tumors (tumor-repopulating cells (TRCs)). PCK2 downregulation accelerated biosynthesis and transportation of citrate from mitochondria to the cytosol, leading to cytosolic glucose carbon flow via OAA-malate-pyruvate and acetyl-CoA-fatty acid pathways in TRCs. On the other hand, downregulating PCK2 hindered fumarate carbon flows in TCA cycle, leading to attenuated oxidative phosphorylation. In pathological terms, PCK2 overexpression slowed TRC growth in vitro and impeded tumorigenesis in vivo. Overall, our work unveiled unexpected glucose carbon flows of TRCs in melanoma that have implications for targeting metabolic aspects of melanoma.

A La(2/3)Ca(1/3)MnO(3) Hall bar with its long dimension roughly along the hard axis [110] was fabricated on a single-crystal-like tensilely strained film on SrTiO(3)(001). The anisotropic magnetoresistance (AMR) and planar Hall effect (PHE) have been studied at various external magnetic fields and temperatures. A phenomenological model in the high field limit is developed, and the galvanomagnetic tensor based on a tetragonal symmetry 4/mmm (D(4h)), applicable to epitaxial films on a substrate, has been obtained by expanding the tensor to the sixth order. The derived in-plane transverse resistance R(xy) shows a sin2φ(M) angular dependence, while the longitudinal R(xx) is constituted by not only a two-fold cos2φ(M) term, but also a four-fold cos4φ(M) term due to the square symmetry of the lattice. The model is in good agreement with the experimental results in high fields, while deviations are observed near the {100} easy axis with the decreasing field. Close inspection of the fitting parameters reveals the evolution of these term weights with temperature and magnetic field, which is distinct from conventional ferromagnetic metals and cannot be explained by the phenomenological model. An alternative mechanism for AMR, stemming from the magnetization-induced local orbit deformation through spin-orbit interaction, as previously proposed by O'Donnell et al, may be prevalent in manganites and other systems of complicated crystal structure.

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Hepatocytes have been successfully generated from human pluripotent stem cells (hPSCs). However, the cost-effective and clinical-grade generation of hepatocytes from hPSCs still need to be improved. In this study, we reported the production of functional hepatocytes from clinical-grade human embryonic stem cells (hESCs) under good manufacturing practice (GMP) requirements. We sequentially generated primitive streak (PS), definitive endoderm (DE), hepatoblasts and hepatocyte-like cells (HLCs) from hESCs in the different stages with completely defined reagents. During hepatoblast differentiation, dimethyl sulfoxide (DMSO), transferrin, L-ascorbic acid 2-phosphate sesquimagnesium salt hydrate (Vc-Mg), insulin, and sodium selenite were used instead of cytokines and FBS/KOSR. Then, hepatoblasts were differentiated into HLCs that had a typical hepatocyte morphology and possessed characteristics of mature hepatocytes, such as metabolic-related gene expression, albumin secretion, fat accumulation, glycogen storage, and inducible cytochrome P450 activity in vitro. HLCs integrated into the livers of Tet-uPA Rag2–/– Il2rg–/– (URG) mice, which partially recovered after transplantation. Furthermore, a series of biosafety-related experiments were performed to ensure future clinical applications. In conclusion, we developed a chemically defined system to generate qualified clinical-grade HLCs from hESCs under GMP conditions. HLCs have been proven to be safe and effective for treating liver failure. This efficient platform could facilitate the treatment of liver diseases using hESC-derived HLCs transplantation.

Summary Background Dermoscopy and reflectance confocal microscopy (RCM) are noninvasive techniques for the diagnosis of skin lesions. Their accuracy for amelanotic/hypomelanotic melanoma (AHM) has not been systematically studied. Objectives We aimed to investigate systematically the accuracy of dermoscopy and RCM and to compare the accuracy between them for diagnosing AHM. Methods We searched the PubMed, Web of Science, Embase and Cochrane Library databases for eligible studies about dermoscopy, RCM and AHM from inception to 31 June 2019. The quality of the studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool. The pooled results were calculated using a random effects model in Stata 14, Meta‐DiSc, RevMan 5·3 and SAS 9·4. We also explored the sources of heterogeneity by sensitivity analysis. Results Seven studies with a total of 1111 lesions were included. The pooled sensitivity and specificity of dermoscopy for the diagnosis of AHM were 61% [95% confidence interval (CI) 0·37–0·81] and 90% (95% CI 0·74–0·97), respectively. The corresponding respective values of RCM for the diagnosis of AHM were 67% (95% CI 0·51–0·81) and 89% (95% CI 0·86–0·92). In three studies including the performance of both RCM and dermoscopy, the relative diagnostic odds ratio of RCM over dermoscopy was 4·69 (95% CI 0·81–27·3) (P = 0·068). Conclusions Our study demonstrates that both dermoscopy and RCM offer good diagnostic accuracy with high specificity and moderate sensitivity in the diagnosis of AHM. RCM is more accurate than dermoscopy in diagnosing AHM but the comparison needs to be confirmed. What's already known about this topic? Amelanotic/hypomelanotic melanoma (AHM) is the most lethal skin cancer. The diagnosis of AHM is a great challenge because of its nonspecific clinical manifestation. Early diagnosis can improve the prognosis. Dermoscopy and reflectance confocal microscopy (RCM) have high diagnostic accuracy for pigmented melanoma. What does this study add? Both dermoscopy and RCM offer good diagnostic accuracy with high specificity and moderate sensitivity for AHM. RCM might be more accurate than dermoscopy for diagnosis of AHM. More research on the diagnostic accuracy of dermoscopy and RCM for AHM is required in support of these findings. Linked Comment: Chi. Br J Dermatol 2020; 183:197.

The evolution of topological magnetic domains microscopically correlates the dynamic behavior of memory units in spintronic application. Nanometric bubbles with variation of spin configurations have been directly observed in a centrosymmetric hexagonal magnet (MnNi)(GaY) (y = 0.01) using Lorentz transmission electron microscopy. Magnetic bubbles instead of biskyrmions are generated due to the enhancement of quality factor Q caused by the substitution of rare-earth element Y. Furthermore, the bubble density and diversified spin configurations are systematically manipulated via combining the electric current with perpendicular magnetic fields. The magnetic bubble lattice at zero field is achieved after the optimized manipulation.