Background and Aims
Currently there is no Food and Drug Administration–approved drug to treat NAFLD and NASH, the rates of which are increasing worldwide. Although NAFLD/NASH are highly complex and ...heterogeneous conditions, most pharmacotherapy pipelines focus on a single mechanistic target. Considering the importance of the gut‐liver axis in their pathogenesis, we investigated the therapeutic effect of a long‐acting dual agonist of glucagon‐like peptide (GLP)‐1 and GLP‐2 receptors in mice with NAFLD/NASH.
Approach and Results
C57BL/6J mice were fed a choline‐deficient high‐fat diet/high fructose and sucrose solution. After 16 weeks, mice were randomly allocated to receive vehicle, GLP1‐Fc, GLP2‐Fc, or GLP1/2‐Fc fusion (GLP1/2‐Fc) subcutaneously every 2 days for 4 weeks. Body weight was monitored, insulin/glucose tolerance tests were performed, feces were collected, and microbiome profiles were analyzed. Immobilized cell systems were used to evaluate direct peptide effect. Immunohistochemistry, quantitative PCR, immunoblot analysis, tunnel assay, and biochemical assays were performed to assess drug effects on inflammation, hepatic fibrosis, cell death, and intestinal structures. The mice had well‐developed NASH phenotypes. GLP1/2‐Fc reduced body weight, glucose levels, hepatic triglyceride levels, and cellular apoptosis. It improved liver fibrosis, insulin sensitivity, and intestinal tight junctions, and increased microvillus height, crypt depth, and goblet cells of intestine compared with a vehicle group. Similar effects of GLP1/2‐Fc were found in in vitro cell systems. GLP1/2‐Fc also changed microbiome profiles. We applied fecal microbiota transplantation (FMT) gain further insight into the mechanism of GLP1/2‐Fc–mediated protection. We confirmed that FMT exerted an additive effect on GLP1‐Fc group, including the body weight change, liver weight, hepatic fat accumulation, inflammation, and hepatic fibrosis.
Conclusions
A long‐acting dual agonist of GLP‐1 and GLP‐2 receptors is a promising therapeutic strategy to treat NAFLD/NASH.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
5
d
pyrochlore oxides with all-in-all-out magnetic order are prime candidates for realizing strongly correlated, topological phases of matter. Despite significant effort, a full ...understanding of all-in-all-out magnetism remains elusive as the associated magnetic excitations have proven difficult to access with conventional techniques. Here we report a Raman spectroscopy study of spin dynamics in the all-in-all-out magnetic state of the 5
d
pyrochlore Cd
2
Os
2
O
7
. Through a comparison between the two-magnon scattering and spin-wave theory, we confirm the large single ion anisotropy in this material and show that the Dzyaloshinskii–Moriya and exchange interactions play a significant role in the spin-wave dispersions. The Raman data also reveal complex spin–charge–lattice coupling and indicate that the metal–insulator transition in Cd
2
Os
2
O
7
is Lifshitz-type. Our work establishes Raman scattering as a simple and powerful method for exploring the spin dynamics in 5
d
pyrochlore magnets.
Impurity‐induced structural distortion in SmB6 is suggested by Raman spectroscopy study on impurity‐controlled samples. Significant differences in the Raman spectra of single crystals SmB6(6N), ...synthesized with 99.9999%‐pure boron, and SmB6(3N), synthesized with 99.9%‐pure boron, are detected. While no noticeable differences are detected in the X‐ray diffraction of SmB6(3N) and SmB6(6N), all the Raman phonon modes of the T2g, Eg, and A1g of SmB6(3N) are clearly broader and shift to higher wavenumbers than those of SmB6(6N), and the T2g and Eg modes of SmB6(3N) show doublet features. Based on the high‐pressure Raman measurements and phonon calculation in uniaxial compression model, we argue that small amount of impurities in SmB6(3N) is enough to induce anisotropic distortion in the B6 octahedra, leading to peculiar behaviors in Raman spectrum of SmB6(3N). Our results may present a clue for understanding the current puzzles about SmB6 of various origins with different impurities.
Significant differences in the Raman spectra of single crystals SmB6(6N), synthesized with 99.9999%‐pure boron, and SmB6(3N), synthesized with 99.9%‐pure boron, are detected. We argue that small amount of impurities in SmB6(3N) can induce anisotropic distortion in the B6 octahedra, leading to peculiar behaviors in its Raman spectrum.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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•A strong Raman intensity enhancement of the two-magnon (2 M) mode was observed in the NiO nanoparticles annealed in vacuum.•The increased 2 M peak intensity is microscopically ...explained by the increasing proportion of octahedral NiO6 symmetry.•Varied oxygen environment underlie both the change in the 2 M intensity and the splitting of TO phonon of NiO nanoparticles.
Nanostructured antiferromagnetic (AFM) NiO has attracted much attention from both the fundamental and applied perspectives. Understanding the two-magnon (2 M) is of great significance in NiO applications such as spin valves and next-generation magnetic random access memories (MRAM). We investigated the phonon modes and antiferromagnetically ordered states of NiO nanoparticles prepared by empirically controlled measurements. An intensity enhancement of the 2 M mode was observed by Raman spectroscopy as the NiO nanoparticles were vacuum annealed at 650 ℃. The increased 2 M peak intensity in NiO nanoparticles is explained by the local symmetry conversions from NiO5 to NiO6 configurations due to the oxygen redistribution during the vacuum annealing. The change of the splitting of anisotropic transverse optical (TO) phonon with different oxygen contents was also revealed by the Raman spectroscopy. We have shown that the changes in the oxygen environment underlie both the change in the 2 M intensity and the splitting of TO phonon in the NiO nanoparticles. Our work offers an efficient avenue to strengthen the AFM ordering and emphasizes the effect of vacuum annealing of the NiO nanoparticles, opening the interesting possibility of individual parameter control in practical applications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Optical control of the spin degree of freedom is often desired in application of the spin technology. Here we report spin-rotational excitations observed through inelastic light scattering ...of the hexagonal LuMnO
3
in the antiferromagnetically (AFM) ordered state. We propose a model based on the spin–spin interaction Hamiltonian associated with the spin rotation of the Mn ions, and find that the spin rotations are angularly quantized by 60°, 120°, and 180°. Angular quantization is considered to be a consequence of the symmetry of the triangular lattice of the Mn-ion plane in the hexagonal LuMnO
3
. These angularly-quantized spin excitations may be pictured as isolated flat bubbles in the sea of the ground state, which may lead to high-density information storage if applied to spin devices. Optically pumped and detected spin-excitation bubbles would bring about the advanced technology of optical control of the spin degree of freedom in multiferroic materials.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Human granulocyte colony-stimulating factor (G-CSF, this study used Fc-fused recombinant G-CSF; GX-G3) is an important glycoprotein that stimulates the proliferation of granulocytes and ...white blood cells. Thus, G-CSF treatment has been considered as a crucial regimen to accelerate recovery from chemotherapy-induced neutropenia in cancer patients suffering from non-myeloid malignancy or acute myeloid leukemia. Despite the therapeutic advantages of G-CSF treatment, an assessment of its immunogenicity must be performed to determine whether the production of anti-G-CSF antibodies causes immune-related disorders. We optimized and validated analytical tools by adopting validation parameters for immunogenicity assessment. Using these validated tools, we analyzed serum samples from rats and monkeys injected subcutaneously with GX-G3 (1, 3 or 10 mg/kg once a week for 4 weeks followed by a 4-week recovery period) to determine immunogenicity response and toxicokinetic parameters with serum concentration of GX-G3. Several rats and monkeys were determined to be positive for anti-GX-G3 antibodies. Moreover, the immunogenicity response of GX-G3 was lower in monkeys than in rats, which was relevant to show less inhibition of toxicokinetic profiles in monkeys, at least 1 mg/kg administrated group, compared to rats. These results suggested the establishment and validation for analyzing anti-GX-G3 antibodies and measurement of serum levels of GX-G3 and anti-GX-G3 antibodies, which was related with toxicokinetic profiles. Taken together, this study provides immunogenicity assessment which is closely implicated with toxicokinetic study of GX-G3 in 4-week repeated administrated toxicological studies.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Growing demands for ultra‐fast switching of spins have turned attention to optically controlled spintronics, which indeed has recently been demonstrated promising. Here we report localized spin‐flip ...excitations revealed by resonance inelastic light scattering on hexagonal holmium manganite thin films with the magnetic manganese ions substituted by the nonmagnetic gallium ions (HoMn1 − xGaxO3). Our analyses on a broad Raman peak support that the corresponding spin excitation is associated with flipping of all three Mn3+ spins in the elementary trimer of manganese ions and hence maintains the same excitation energy determined by the intrinsic spin–spin interaction between Mn3+ ions. The nonmagnetic gallium ions only reduce the population of the spin excitations by breaking the spin‐frustrated triangular network. Such localized spin‐flip excitations show another promise towards optically controlled spin devices.
The origin of the spin excitations in the hexagonal HoMnO3 below the Néel ordering temperature is investigated by resonance inelastic light scattering. Our analyses on experimental data along with theoretical modeling on the spin‐excitation peak support that the corresponding spin excitations are associated with flipping of all three Mn3+ spins in the elementary trimer of manganese ions. The spin‐flip excitations are limited in the Mn triangular network. Such localized spin‐flip excitations show another promise towards optically controlled spin devices.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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•Discovered spin-dependent Raman scattering modes in the Raman spectra of the MPSe3 (M = Fe, Mn).•Analyzed the intensity variations of the spin-dependent Raman scattering modes in ...MPSe3 using the Suzuki–Kamimura formalism.•Confirmed the 2D Ising characteristic in FePSe3 by comparing the spin correlation function and the reduced magnetization.
Magnetism in van der Waals (vdW) materials has recently garnered significant attention due to their potential for advanced applications. In this study, we investigate the magnetic transition in layered MPSe3 (M = Fe, Mn) bulk flakes utilizing temperature-dependent Raman spectroscopy. Our findings reveal unique features in the Raman spectrum that are strongly correlated with the antiferromagnetic ordering in MPSe3. We analyze the spin-dependent Raman scattering modes in MPSe3 by applying the Suzuki–Kamimura formalism. Consequently, our comparative analyses of the spin correlation function and the reduced magnetization provide compelling evidence of the 2D Ising characteristic especially in FePSe3. Our results clearly show the potential of MPSe3 as a prominent platform for exploring fundamental aspects of low-dimensional magnetism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Free fatty acid (FFA) is one of the most critical parameters for evaluating the quality of olive oil. In this paper, we present a simple and rapid Raman spectroscopy method for analyzing free fatty ...acid in olive oil. First, FFA degradation of carotenoids in olive oil is confirmed by analyzing the relative intensity of characteristic vibrational modes and introducing an intensity decrease factor. Second, it is demonstrated that the relative intensity ratio of the two characteristic vibrational modes at 1525 cm−1 and 1655 cm−1 presents a good and rapid analysis of FFA content in olive oil; the relative intensity ratio decreases linearly with FFA content. In addition, resonance Raman scattering of carotenoid is discussed, showing that a green laser should be utilized to study FFA in olive oil.
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