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We previously synthesized cysteine-installed C-terminally PEGylated oligolysines with 20 amino acid residues to form cross-linked polymeric micelles (PMs) with luciferase-coding plasmid DNA as a candidate for artificial gene vectors. Luciferase gene expression in HeLa cells mediated by PEG-CK

Objectives Currently, no indicators on which biologic disease-modifying anti-rheumatic drugs (bDMARDs) should be used first for juvenile idiopathic arthritis (JIA) have been established. Thus, this study aimed to determine the useful biomarkers in JIA to enable the best selection of the first bDMARDs without primary failure. Methods This retrospective study used data of patients examined for JIA between 2015 and 2021 at Kagoshima University Hospital in Japan. Results Altogether, 67 cases of non-systemic JIA were analyzed, excluding cases that had been treated for Conclusions RF+ JIA required bDMARDs with high probability. JIA with high titre of RF tends to be refractory to anti-TNFα agents. Tocilizumab or abatacept could be a first-choice bDMARD in such cases.

This article presents a prototype $22.4~\mu \text{m}$ pixel pitch global shutter (GS) wide dynamic range (WDR) soft X-ray CMOS image sensor (sxCMOS). Backside-illuminated (BSI) pinned photodiodes with a 45- $\mu \text{m}$ thick Si substrate were introduced for low noise and high radiation hardness to high energy photons. Two-stage lateral overflow integration capacitor (LOFIC) and voltage domain memory bank with high-density Si trench capacitors were introduced for WDR and for GS. The developed sxCMOS achieved maximum 21.9 Me− full well capacity with a single exposure 129 dB dynamic range by GS operation. Over 70% quantum efficiency (QE) toward soft X-ray was successfully achieved. The developed prototype sxCMOS is a step forward toward a 4 M pixel detector system to be utilized in next-generation synchrotron radiation facilities and X-ray free-electron lasers.

Magnetic skyrmion is a topologically protected particle-like object in magnetic materials, appearing as a nanometric swirling spin texture. The size and shape of skyrmion particles can be flexibly controlled by external stimuli, which suggests unique features of their crystallization and lattice transformation process. Here, we investigated the detailed mechanism of structural transition of skyrmion lattice (SkL) in a prototype chiral cubic magnet Cu2OSeO3, by combining resonant soft X-ray scattering (RSXS) experiment and micromagnetic simulation. This compound is found to undergo a triangular-to-square lattice transformation of metastable skyrmions by sweeping magnetic field (B). Our simulation suggests that the symmetry change of metastable SkL is mainly triggered by the B-induced modification of skyrmion core diameter and associated energy cost at the skyrmion-skyrmion interface region. Such internal deformation of skyrmion particle has further been confirmed by probing the higher harmonics in the RSXS pattern. These results demonstrate that the size/shape degree of freedom of skyrmion particle is an important factor to determine their stable lattice form, revealing the exotic manner of phase transition process for topological soliton ensembles in the non-equilibrium condition., Skyrmions are topological spin textures and are of great interest due to their impressive stability. Here, by sweeping an applied magnetic field, the authors observe a change in the skyrmion lattice structure, shedding light on the relation between skyrmion size and stability.

Cryopyrin-associated periodic fever syndrome (CAPS) is a highly debilitating disorder, which is characterized by unregulated interleukin-1β production driven by autosomal dominantly inherited mutations in the NLRP3 gene. Patients with CAPS often present with early-onset episodes of fever and rash. These patients also present with variable systemic signs and symptoms, such as arthritis, sensorineural hearing loss, chronic aseptic meningitis, and skeletal abnormalities, but minimal gastrointestinal symptoms. Recently, effective therapies for CAPS targeted against interleukin-1 have become available. We report a case of a young Japanese woman with CAPS who developed inflammatory bowel disease during canakinumab therapy. The patient had colostomy after intestinal perforation and changed canakinumab to infliximab. To the best of our knowledge, this is the first report of a case of inflammatory bowel disease secondary to CAPS complicated by gastrointestinal symptoms and arthritis which canakinumab could not control. Patients with CAPS who have symptoms that cannot be controlled by canakinumab should be considered for possible co-morbidities.

The relationship between the magnetic interaction and photoinduced dynamics in antiferromagnetic perovskites is investigated in this study. In La${}_{1/3}$Sr${}_{2/3}$FeO${}_{3}$ thin films, commensurate spin ordering is accompanied by charge disproportionation, whereas SrFeO${}_{3}$ thin films show incommensurate helical antiferromagnetic spin ordering due to increased ferromagnetic coupling compared to La${}_{1/3}$Sr${}_{2/3}$FeO${}_{3}$. To understand the photoinduced spin dynamics in these materials, we investigate the spin ordering through time-resolved resonant soft X-ray scattering. In La${}_{1/3}$Sr${}_{2/3}$FeO${}_{3}$, ultrafast quenching of the magnetic ordering within 130 fs through a nonthermal process is observed, triggered by charge transfer between the Fe atoms. We compare this to the photoinduced dynamics of the helical magnetic ordering of SrFeO${}_{3}$. We find that the change in the magnetic coupling through optically induced charge transfer can offer an even more efficient channel for spin-order manipulation., 7 pages, 5 figures

We systematically synthesized perovskite-type oxides Sr1-xCaxCoO3 containing unusually high valence Co4+ ions by a high pressure technique, and investigated the effect of systematic lattice change on the magnetic and electronic properties. As the Ca content x exceeds about 0.6, the structure changes from cubic to orthorhombic, which is supported by the first-principles calculations of enthalpy. Upon the orthorhombic distortion, the ground state remains to be apparently ferromagnetic with a slight drop of the Curie temperature. Importantly, the compounds with x larger than 0.8 show antiferromagnetic behavior with positive Weiss temperatures and nonlinear magnetization curves at lowest temperature, implying that the ground state is noncollinear antiferromagnetic or helimagnetic. Considering the incoherent metallic behavior and the suppression of the electronic specific heat at high x region, the possible emergence of a helimagnetic state in Sr1-xCaxCoO3 is discussed in terms of the band-width narrowing and the double-exchange mechanism with the negative charge transfer energy as well as the spin frustration owing to the next-nearest neighbor interaction., Comment: 13 pages, 4 figures

To stabilize small interfering RNA (siRNA) in the bloodstream for systemic RNAi therapeutics, we previously fabricated ultrasmall siRNA nanocarriers that were sub-20 nm in hydrodynamic diameter, named as unit polyion complexes (uPICs), using two-branched poly(ethylene glycol)

Development of efficient delivery vehicles for in vitro transcribed mRNA (IVT mRNA) is currently a major challenge in nanomedicines. For systemic mRNA delivery, we developed a series of cationic amphiphilic polyaspartamide derivatives (PAsp(DET/R)s) carrying various alicyclic (R) moieties with diethylenetriamine (DET) in the side chains to form mRNA-loaded polyplexes bearing stability under physiological conditions and possessing endosomal escape functionality. While the size and ζ-potential of polyplexes were comparable among various PAsp(DET/R)s, the transfection efficiencies of polyplexes were considerably varied due to difference in the R moieties of PAsp(DET/R)s and were described by an octanol-water (or buffer at pH 7.3) distribution coefficient (logD

${\mathrm{Cd}}_{3}{\mathrm{As}}_{2}$ is one of the prototypical topological Dirac semimetals. Here, we manipulate the band inversion responsible for the emergence of Dirac nodes by alloying ${\mathrm{Cd}}_{3}{\mathrm{As}}_{2}$ with topologically trivial ${\mathrm{Zn}}_{3}{\mathrm{As}}_{2}$. The carrier density monotonically decreases and the resistivity is enhanced as $x$ is increased. For larger $x$, the thermoelectric figure of merit exhibits comparably large values exceeding 0.3 at room temperature, due to the combined effects of a strong enhancement of the thermopower, an only moderate increase in the resistivity, and a suppression of the thermal conductivity. Complementary quantum-oscillation data and optical-conductivity measurements allow us to infer that the Dirac nodes are gapped out, and a band structure with a partly flat dispersion likely emerges in the higher-$x$ region in ${\mathrm{Cd}}_{3\ensuremath{-}x}{\mathrm{Zn}}_{x}{\mathrm{As}}_{2}$.

Oligolysine-based PEG-peptides with 15 or 20 amino acid residues including two cysteines were synthesized to formulate cross-linked polyplex micelles (PMs) incorporating luciferase-coding plasmid DNA (pDNA). Two cysteine residues were separately allocated at the C-terminal, center, or N-terminal of peptide moieties. Although TEM observation showed that all PEG-peptides condensed pDNA into rod-like or toroidal morphologies, the rod length distribution of PMs was affected by both the amino acid sequence and the peptide length of PEG-peptides. In comparison to the cysteine-uninstalled PEG-peptides, the cysteine-installed PEG-peptides exhibited a reductive environment-responsive pDNA release, which was observed in a gel retardation assay. From physicochemical characterizations, a relationship between the amino acid sequence and the in vitro gene expression efficacy of PMs in a cell-free protein synthesis system has been clearly demonstrated. Finally, the cell-based assay using HeLa cells has been tested, and the differences between both results of cell-free and cell-based systems are discussed.

A new perovskite-type cuprate PrCuO3 has been synthesized by high-pressure oxygen annealing. Synchrotron X-ray powder diffraction and absorption spectroscopy revealed that PrCuO3 crystallizes in the GdFeO3-type structure with cooperative Jahn–Teller distortion, forming one-dimensional chains of corner-shared CuO4 plaquettes with nearly divalent Cu ions.

Systemic juvenile idiopathic arthritis (sJIA) has recently become regarded as one of the autoinflammatory syndromes (AIS). However, other AIS, such as familial Mediterranean fever (FMF) and Blau syndrome, have been initially misdiagnosed as sJIA because of the clinical similarities. Making the correct diagnosis in the early stage of these AIS is desirable. Therefore, we evaluated serum S100A12 and vascular endothelial growth factor (VEGF) levels to determine if they could be biomarkers for differentiating these AIS. Serum S100A12 and VEGF levels were examined in patients with Blau syndrome (n = 4), FMF (n = 4), and sJIA (n = 11) in the active and inactive phases. In the active phase, S100A12 levels were significantly higher in patients with sJIA and FMF compared with those with Blau syndrome (p

A layered perovskite-type oxide ${\mathrm{Ba}}_{2}{\mathrm{RhO}}_{4}$ was synthesized by a high-pressure technique with the support of convex-hull calculations. The crystal and electronic structure were studied by both experimental and computational tools. Structural refinements for powder x-ray diffraction data showed that ${\mathrm{Ba}}_{2}{\mathrm{RhO}}_{4}$ crystallizes in a ${\mathrm{K}}_{2}{\mathrm{NiF}}_{4}$-type structure, isostructural to ${\mathrm{Sr}}_{2}{\mathrm{RuO}}_{4}$ and ${\mathrm{Ba}}_{2}{\mathrm{IrO}}_{4}$. Magnetic, resistivity, and specific-heat measurements for polycrystalline samples of ${\mathrm{Ba}}_{2}{\mathrm{RhO}}_{4}$ indicate that the system can be characterized as a correlated metal. Despite the close similarity to its ${\mathrm{Sr}}_{2}{\mathrm{RuO}}_{4}$ counterpart in the electronic specific-heat coefficient and the Wilson ratio, ${\mathrm{Ba}}_{2}{\mathrm{RhO}}_{4}$ shows no signature of superconductivity down to 0.16 K. Whereas the Fermi surface topology has reminiscent pieces of ${\mathrm{Sr}}_{2}{\mathrm{RuO}}_{4}$, an electronlike ${e}_{\mathrm{g}}\ensuremath{-}({d}_{{x}^{2}\ensuremath{-}{y}^{2}})$ band descends below the Fermi level, making this compound unique also as a metallic counterpart of the spin-orbit coupled Mott insulator ${\mathrm{Ba}}_{2}{\mathrm{IrO}}_{4}$.

In this chapter, we review the recent research on the spin-state ordering in epitaxial thin films of perovskite LaCoO3 from the viewpoint of optical spectroscopy and X-ray scattering. A remarkable feature is that a variety of spin/orbital orderings, which have not been identified in bulk samples, can be induced by tuning the epitaxial strain in thin film samples. In the moderately tensile-strained films, a spin-state/orbital ordering accompanying the ordering of high-spin-state site and low-spin-state site occurs around 130 K, and subsequently, a ferromagnetic/ferrimagnetic ordering emerges around 90 K. In the weakly strained films, another spin-state/orbital ordered phase with longer modulation period emerges around 40 K, followed by a ferromagnetic ordering transition around 20 K. By analyzing the Co-3d orbital state by the resonant soft X-ray scattering technique, we identified that two kinds of high-spin state with different site symmetries emerges in this phase. Moreover, by means of grazing-incidence resonant soft X-ray scattering technique, it is demonstrated that the transition temperature of spin-state ordering is higher in the surface-layer of film than inside the film due to the strain relaxation. These results demonstrate that the strain engineering of epitaxial thin films offers a fertile playground to study the spin-state/orbital ordering in the correlated spin-crossover material.

We demonstrate inline holography with a soft-x-ray vortex beam having an orbital angular momentum. A hologram is recorded as an interference pattern between a Bragg-diffracted wave from a fork grating and a divergent wave generated by a Fresnel zone plate. The images obtained exhibit fork-shaped interference fringes, which confirm the formation of a vortex beam. By analyzing the interference images, we successfully obtain a spiral phase distribution with a topological charge $\ensuremath{\ell}=\ifmmode\pm\else\textpm\fi{}1$. The results demonstrate that the inline-holography technique may be an effective probe for the characterization of topological defects in magnetic textures.

A detailed electronic phase diagram of perovskite-type oxides ${\mathrm{Sr}}_{1--x}{\mathrm{La}}_{x}\mathrm{Fe}{\mathrm{O}}_{3}$ ($0\ensuremath{\leqq}x\ensuremath{\leqq}0.5$) was established by synchrotron x-ray diffraction, magnetization, and transport measurements for polycrystalline samples synthesized by a high-pressure technique. Among three kinds of helimagnetic phases in $\mathrm{SrFe}{\mathrm{O}}_{3}$ at zero field, two of them showing multiple-$\mathbit{q}$ helimagnetic spin textures tend to rapidly disappear in cubic symmetry upon the La substitution with $x$ less than 0.1, which accompanies the loss of metallic nature. On the other hand, the third helimagnetic phase apparently remains robustly in ${\mathrm{Sr}}_{1--x}{\mathrm{La}}_{x}\mathrm{Fe}{\mathrm{O}}_{3}$ with $x$ higher than 0.1, followed by merging to the spin/charge ordered phase with $x\ensuremath{\sim}1/3$. We propose an important role of itinerant ligand holes on the emergence of multiple-$\mathbit{q}$ states and a possible link between the third (putative single-$\mathbit{q}$) helimagnetic phase in $\mathrm{SrFe}{\mathrm{O}}_{3}$ and the spin/charge ordered phase in ${\mathrm{Sr}}_{2/3}{\mathrm{La}}_{1/3}\mathrm{Fe}{\mathrm{O}}_{3}$.

Background Blau syndrome (BS) is an autoinflammatory disease associated with mutations in nucleotide-binding oligomerization domain 2. Although treatments with anti-TNF agents have been reported to be effective, the underlying molecular mechanisms remain unclear. Objective We aimed to elucidate the mechanisms of autoinflammation in patients with BS and to clarify how anti-TNF treatment controls the disease phenotype at the cellular level in clinical samples. Methods Macrophages were differentiated from monocytes of 7 BS patients, and global transcriptional profiles of 5 patients were analyzed with or without IFN-γ stimulation. Macrophages were also generated from BS-specific induced pluripotent stem cells (iPSCs), and their transcriptome was examined for comparison. Results Aberrant inflammatory responses were observed upon IFN-γ stimulation in macrophages from untreated BS patients, but not in those from patients treated with anti-TNF. iPSC-derived macrophages carrying a disease-associated mutation also showed IFN-γ–dependent accelerated inflammatory responses. Comparisons of peripheral blood– and iPSC-derived macrophages revealed the upregulation of nuclear factor kappa–light-chain enhancer of activated B cells (NF-κB) targets in unstimulated macrophages as a common feature. Conclusions IFN-γ stimulation is one of the key signals driving aberrant inflammatory responses in BS-associated macrophages. However, long-term treatment with anti-TNF agents ameliorates such abnormalities even in the presence of IFN-γ stimulation. Our data thus suggest that preexposure to TNF or functionally similar cytokines inducing NF-κB–driven proinflammatory signaling during macrophage development is a prerequisite for accelerated inflammatory responses upon IFN-γ stimulation in BS.

The topological Hall effect (THE) and its thermoelectric counterpart, the topological Nernst effect (TNE), are hallmarks of the skyrmion lattice phase (SkL). We observed the giant TNE of the SkL in centrosymmetric Gd$_2$PdSi$_3$, comparable in magnitude to the largest anomalous Nernst signals in ferromagnets. Significant enhancement (suppression) of the THE occurs when doping electrons (holes) to Gd$_2$PdSi$_3$. On the electron-doped side, the topological Hall conductivity approaches the characteristic threshold $\sim 1000\,\left(\mathrm{\Omega cm}\right)^{-1}$ for the intrinsic regime. We use the filling-controlled samples to confirm Mott's relation between TNE and THE and discuss the importance of Gd-5d orbitals for transport in this compound., Comment: Main text: 9 pages, 4 figures; with SI: 36 pages, 15 figures

In this study, the magnetic field effect was investigated on the magnetic and electric properties of a chiral-polar-ordered corundum, ${\mathrm{Ni}}_{2}\mathrm{InSb}{\mathrm{O}}_{6}$. Single-crystal soft x-ray and neutron diffraction measurements were used to verify the magnetic modulations with long wavelengths. The modulation direction tends to align along the magnetic field when it is applied perpendicular to the polar axis, suggesting that the nearly proper-screw-type helicoid should be formed below 77 K owing to the dominant activation of chirality-induced uniform Dzyaloshinskii-Moriya interactions despite the existence of both chirality and polarity. When a high magnetic field is applied perpendicular to the polar axis, a helix-to-canted antiferromagnetic transition is observed through the intermediate soliton lattice type state. In contrast, a magnetic field applied along the polar axis induces a first-order metamagnetic transition. These metamagnetic transitions accompany a change in the electric polarization along the polar axis.

The tensile strain is a promising tool for creation and manipulation of magnetic solitonic textures in the chiral helimagnets via tunable control of magnetic anisotropy and Dzyaloshinskii-Moriya interaction. Here, by using the in-situ resonant small-angle x-ray scattering we demonstrate that the skyrmion and chiral soliton lattices can be achieved as metastable states in FeGe lamella as distinct states or even simultaneously by combining the tensile strain and magnetic fields in various orientations with respect to the deformation. The small-angle scattering data are discussed in the frame of the analytical model which is sufficient to describe the experimental results for soliton lattice. By using the experimental results and analytical theory, unwinding of the metastable skyrmions in the perpendicular magnetic field as seen by small-angle scattering experiment was analyzed by the micromagnetic simulation.

For the skyrmion-hosting intermetallic Gd$_2$PdSi$_3$ with centrosymmetric hexagonal lattice and triangular net of rare earth sites, we report a thorough investigation of the magnetic phase diagram. Our work reveals a new magnetic phase with isotropic value of the critical field for all orientations, where the magnetic ordering vector $\mathbf{q}$ is depinned from its preferred directions in the basal plane. This is in contrast to the highly anisotropic behavior of the low field phases, such as the skyrmion lattice (SkL), which are easily destroyed by in-plane magnetic field. The bulk nature of the SkL and of other magnetic phases was evidenced by specific-heat measurements. Resistivity anisotropy, likely originating from partial gapping of the density of states along $\mathbf{q}$ in this RKKY magnet, is picked up via the planar Hall effect (PHE). The PHE confirms the single-$\mathbf{q}$ nature of the magnetic order when the field is in the hexagonal plane, and allows to detect the preferred directions of $\mathbf{q}$. For field aligned perpendicular to the basal plane, several scenarios for the depinned phase (DP), such as tilted conical order, are discussed on the basis of the data., 27 pages, 12 figures (including SI)

Magnetic skyrmions are topologically stable spin swirls with particle-like character and potentially suitable for the design of high-density information bits. While most known skyrmion systems arise in noncentrosymmetric systems with Dzyaloshinskii-Moriya interaction, also centrosymmetric magnets with a triangular lattice can give rise to skyrmion formation, with geometrically-frustrated lattice being considered essential in this case. Until today, it remains an open question if skyrmions can also exist in the absence of both geometrically-frustrated lattice and inversion symmetry breaking. Here, we discover a square skyrmion lattice state with 1.9 nm diameter skyrmions in the centrosymmetric tetragonal magnet GdRu2Si2 without geometrically-frustrated lattice by means of resonant X-ray scattering and Lorentz transmission electron microscopy experiments. A plausible origin of the observed skyrmion formation is four-spin interactions mediated by itinerant electrons in the presence of easy-axis anisotropy. Our results suggest that rare-earth intermetallics with highly-symmetric crystal lattices may ubiquitously host nanometric skyrmions of exotic origins., Accepted to be published in Nature Nanotechnology

MnSi is a prototypical chiral cubic magnet, in which swirling magnetic objects referred to as magnetic skyrmions appear. It is expected that the thin film of MnSi may expand the range of the magnetic skyrmion lattice phase in the temperature--magnetic field diagram. On the other hand, the MnSi film on an achiral Si (111) substrate may suffer from chiral twin formation. We succeeded in visualizing the domain structure of the chirality and axis orientation of a MnSi thin film by using a combination of transmission electron microscopy and x-ray reflectivity measurement. Only two types of domains were found on a Si (111) substrate. The information is essential for the challenge of homochiral film fabrication.

Objectives To assess the performance of the EULAR/ACR idiopathic inflammatory myopathies (IIMs) classification criteria to classify juvenile IIMs (JIIMs) in an Asian paediatric population. Methods Sixty-eight JIIM patients and 49 non-JIIM patients diagnosed at seven major paediatric rheumatology centres in Japan between 2008 and 2015 were enrolled. Retrospective data were collected, and each patient’s data form was submitted. The expert group reviewed the forms and re-examined the diagnoses. The EULAR/ACR criteria were then applied and the probability of having JIIM was determined for each case. The sensitivity and specificity of the EULAR/ACR criteria were compared with those of other existing criteria. Results The sensitivity/specificity of the EULAR/ACR classification criteria were 92.1/100% with muscle biopsy data (n = 38); 86.7/100% without muscle biopsy data (n = 30) and 89.7/100% in our total cohort (n = 68). The sensitivity of Bohan and Peter’s criteria and Tanimoto’s criteria were 80.9 and 64.7% in our total cohort, respectively. Among 68 physician-diagnosed JIIM patients, seven cases (three JDM and four overlap myositis) were not classified as JIIM because the probability did not reach the cut-off point (55%). The three JDM patients all presented with only one of the three skin manifestations that are listed in the criteria: Gottron’s sign. Conclusion Our validation study with Japanese JIIM cases indicates that the EULAR/ACR classification criteria for IIM generally perform better than existing diagnostic criteria for myositis.

To estimate target of treatment for long-term efficacy of the first biologic agent used to treat polyarticular juvenile idiopathic arthritis (pJIA).A retrospective cohort of patients with pJIA treated at six medical institutions in Japan between 1 March 2005 and 31 October 2014 was identified. The patients were divided by 2-year treatment periods with the first biologic agent into continuous treatment group and switching group. Three markers were examined: matrix metalloproteinase-3 (MMP-3), erythrocyte sedimentation rate (ESR), and disease activity score (DAS) 28-ESR.Thirty-two pJIA patients (8 boys, 24 girls) from 43 recruited patients were included in this study. The treatment periods with the first biologic agent in continuous treatment group (24 patients, 75%) was 40 months (median, range 24-119) and switching group (8 patients; 25%) was 9.5 months (median, 6-18). Markers [odds ratio (95% confidence interval)] at 3 months were MMP-3 [1.02 (0.99-1.05), p = .219], ESR [1.00 (0.78-1.30), p = .998], and DAS28-ESR [13.9 (2.08-409.82), p = .035]. The cut-off point for DAS28-ESR at 3 months to distinguish the two groups was 2.49 (sensitivity, 87.5%; specificity, 87.5%).DAS28-ESR of 2.49 at 3 months after initiating the first biologic agent can be a target of sustained treatment in pJIA patients.

Phalangeal microgeodic syndrome is a rare but benign disorder that affects the fingers of children. Ultrasonographic imaging was performed on an 11-year-old female presenting with a 3-week history ...

Structural stability of polyplex micelles (PMs), prepared from plasmid DNA (pDNA) and poly(ethylene glycol)- b -poly( l -lysine) block catiomer (PEG−PLys), was evaluated in terms of their resistance against shear stress. When exposed to shear stress at magnitudes typically present in the blood stream, structural deterioration was observed in PMs owing to the partial removal of PEG−PLys strands. Eventually, impaired PEG coverage of the polyplex core led to accelerated degradation by nucleases, implying that structural deterioration by shear stress in blood stream may be a major cause of rapid clearance of PMs from blood circulation. To address this issue, introduction of disulfide crosslinking into the PM core was shown to be an efficient strategy, which successfully mitigated unfavorable effects of shear stress. Furthermore, improved in vivo blood retention profile and subsequently enhanced antitumor efficacy in systemic treatment of pancreatic adenocarcinoma were confirmed for the crosslinked PMs loaded with pDNA encoding an anti-angiogenic protein, suggesting that high stability under the shear stress during blood circulation may be a critical factor in systemically applicable gene delivery systems.

Magnetic skyrmions are topologically stable spin swirls with a particle-like character and are potentially suitable for the design of high-density information bits. Although most known skyrmion systems arise in non-centrosymmetric systems with a Dzyaloshinskii-Moriya interaction, centrosymmetric magnets with a triangular lattice can also give rise to skyrmion formation, with a geometrically frustrated lattice being considered essential in this case. Until now, it remains an open question if skyrmions can also exist in the absence of both geometrically frustrated lattice and inversion symmetry breaking. Here we discover a square skyrmion lattice state with 1.9 nm diameter skyrmions in the centrosymmetric tetragonal magnet GdRu

Lymphatic malformation (LM) is a congenital disorder resulting from an abnormal development of lymphatic vessels. LM may result in problems of cosmesis and functional impairment, including airway compression. An 11-year-old girl was referred to our department with increasing dysphagia caused by a large left cervical LM with a long history of treatment. Because of the LM location, surgical resection was not an option, and various therapies, including use of picibanil, had proven ineffective. Celecoxib treatment (100 mg/day) was initiated for local pain management. Softening of the lesion was observed 2 weeks after treatment initiation, and the dose was increased to 200 mg/day with additional shrinking of the LM over the next 2 weeks. With parental consent, celecoxib was continued, with a 65% reduction in volume achieved at 6 months. The patient discontinued treatment at 12 months, and the LM volume increased. Control over the LM was achieved with resumption of celecoxib treatment. After 2 years of treatment, the LM persists, but the size of the malformation is significantly smaller. No adverse effects of celecoxib treatment were observed. The anti–cyclooxygenase-2 effect of celecoxib prevented lymphatic vessel growth through an inhibition of cyclooxygenase-2 activity in the conversion of prostaglandin to prostaglandin E2. In conclusion, celecoxib may be a promising therapeutic agent for LM management.

A new perovskite-type cuprate PrCuO