Hydrogen-Bonded Metal-Organic Framework Nanosheet as a Proton Conducting Membrane for an H2 /O2 Fuel Cell.

Proton-conducting metal-organic frameworks (MOFs) have attracted attention as potential electrolytes for fuel cells. However, research progress in utilizing MOFs as electrolytes for fuel cells has been limited, mainly due to challenges associated with issues such as the fabrication of MOF membranes, and hydrogen crossover through the MOF's pores. Here, we report proton conductivity and fuel cell performance of a self-standing membrane prepared from of a bismuth subgallate MOF nanosheets with non-porous structure are reported. The fabricated MOF nanosheet membrane with no binding agent exhibitsed structural anisotropy. The proton conductivity in the membrane thickness direction (4.4 × 10-3  S cm-1 ) at 90 °C and RH 100% is observed to be higher than that in the in-plane direction of the membrane (3.3 × 10-5  S cm-1 ). The open circuit voltage (OCV) of a fuel cell with ≈120 µm proton conducting membrane is 1.0 V. The non-porous nature of the MOF nanosheets contributes to the relatively high OCV. A fuel cell using ≈40 µm membrane as proton conducting electrolyte records a maximum of 25 mW cm-2 power density and a maximum of 109 mA cm-2 current density with 0.91 V OCV at 80 °C in humid conditions.

Amelioration of nephritis in receptor for advanced glycation end-products (RAGE)-deficient lupus-prone mice through neutrophil extracellular traps.

The receptor for advanced glycation end-products (RAGE) is a pattern recognition receptor that regulates inflammation, cell migration, and cell fate. Systemic lupus erythematosus (SLE) is a chronic multiorgan autoimmune disease. To understand the function of RAGE in SLE, we generated RAGE-deficient (Ager-/-) lupus-prone mice by backcrossing MRL/MpJ-Faslpr/J (MRL-lpr) mice with Ager-/- C57BL/6 mice. In 18-week-old Ager-/- MRL-lpr, the weights of the spleen and lymph nodes, as well as the frequency of CD3+CD4-CD8- cells, were significantly decreased. Ager-/- MRL-lpr mice had significantly reduced urine albumin/creatinine ratios and markedly improved renal pathological scores. Moreover, neutrophil infiltration and neutrophil extracellular trap formation in the glomerulus were significantly reduced in Ager-/- MRL-lpr. Our study is the first to reveal that RAGE can have a pathologic role in immune cells, particularly neutrophils and T cells, in inflammatory tissues and suggests that the inhibition of RAGE may be a potential therapeutic strategy for SLE.

Vanishing and Nonvanishing Persistent Currents of Various Conserved Quantities.

For every conserved quantity written as a sum of local terms, there exists a corresponding current operator that satisfies the continuity equation. The expectation values of current operators at equilibrium define the persistent currents that characterize spontaneous flows in the system. In this Letter, we consider quantum many-body systems on a finite one-dimensional lattice and discuss the scaling of the persistent currents as a function of the system size. We show that, when the conserved quantities are given as the Noether charges associated with internal symmetries or the Hamiltonian itself, the corresponding persistent currents can be bounded by a correlation function of two operators at a distance proportional to the system size, implying that they decay at least algebraically as the system size increases. In contrast, the persistent currents of accidentally conserved quantities can be nonzero even in the thermodynamic limit and even in the presence of the time-reversal symmetry. We discuss "the current of energy current" in S=1/2 XXZ spin chain as an example and obtain an analytic expression of the persistent current.

High-Throughput Investigations of Topological and Nodal Superconductors.

The theory of symmetry indicators has enabled database searches for topological materials in normal conducting phases, which has led to several encyclopedic topological material databases. To date, such a database for topological superconductors is yet to be achieved because of the lack of information about pairing symmetries of realistic materials. In this Letter, sidestepping this issue, we tackle an alternative problem: the predictions of topological and nodal superconductivity in materials for each single-valued representation of point groups. Based on recently developed symmetry indicators for superconductors, we provide comprehensive mappings from pairing symmetries to the topological or nodal superconducting nature for nonmagnetic materials listed in the Inorganic Crystal Structure Database. We quantitatively show that around 90% of computed materials are topological or nodal superconductors when a pairing that belongs to a one-dimensional nontrivial representation of point groups is assumed. When materials are representation-enforced nodal superconductors, positions and shapes of the nodes are also identified. When combined with experiments, our results will help us understand the pairing mechanism and facilitate realizations of the long-sought Majorana fermions promising for topological quantum computations.

Rationale of concomitant cyclophosphamide for remission-induction in patients with antineutrophil cytoplasmic antibody-associated vasculitis: A propensity score-matched analysis of two nationwide prospective cohort studies.

OBJECTIVES: We evaluated the effectiveness of cyclophosphamide for patients with microscopic polyangiitis and granulomatosis with polyangiitis. METHODS: Patients treated with cyclophosphamide and glucocorticoid (cyclophosphamide group) or glucocorticoid alone (non-cyclophosphamide group) for remission-induction were enrolled from two Japanese nationwide prospective inception cohort studies. The effectiveness and safety outcomes were compared before and after propensity score (PS)- matching. RESULTS: Proportion of patients achieving Birmingham Vasculitis Activity Score (BVAS)-remission and BVAS-remission plus a daily prednisolone dosage of ≤10 mg (GC-remission) by Month 6 were not significantly different between cyclophosphamide and non-cyclophosphamide groups before (n = 144 and 155) and after (n = 94 for each group) PS-matching. In myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-positive PS-matched patients, GC-remission by Month 6 was superior in CYC group (n = 82) than in non-CYC group (n = 91) (49 vs. 31%, p = .020). Overall, end-stage renal disease-free and relapse-free survival rates, Vasculitis Damage Index score, and proportions of serious infection were comparable between the two groups both in the unmatched and PS-matched patients. Prednisolone doses at any point after treatment initiation in the PS-matched patients were lower in the cyclophosphamide group than in a non-cyclophosphamide group. CONCLUSIONS: Concomitant cyclophosphamide use may improve GC-remission by Month 6 in MPO-ANCA-positive patients and could exert glucocorticoid sparing effect.

Association of explanatory histological findings and urinary protein and serum creatinine levels at renal biopsy in lupus nephritis: a cross-sectional study.

BACKGROUND: The aim of the present study was to evaluate the association between the histology of active and chronic lesions and urinary protein and serum creatinine (SCr) levels, as common clinical endpoints in clinical trials for lupus nephritis (LN). METHODS: In total, 119 patients diagnosed with LN class III, IV, and V, as defined by the International Society of Nephrology/Renal Pathology Society, between 1990 and 2015, were enrolled in the present study. Multiple regression analysis was performed to explore semi-quantitative histological variables associated with urinary protein and SCr levels. RESULTS: The mean age of the enrolled patients was 45 years, and 79% were female. The mean SCr and mean urinary protein levels at the time of renal biopsy were 0.87 mg/dl and 3.00 g/gCr, respectively. Class IV (71%) was the most common type of LN followed by class III (17%), and class V (13%). Multicollinearity was confirmed between monocellular infiltration (variance inflation factor [VIF] = 10.22) and interstitial fibrosis (VIF = 10.29), and between karyorrhexis (VIF = 4.14) and fibrinoid necrosis (VIF = 4.29). Fibrinoid necrosis and monocellular infiltration were subsequently excluded, and multiple regression analysis revealed that only the urinary protein level was correlated with wire loop lesions (ß-coefficient [ß]: 1.09 and confidence interval [CI]: 0.35 to 1.83), and that the SCr level was correlated with glomerular sclerosis (ß: 1.08 and CI: 0.43 to 1.74). CONCLUSION: As urinary protein and SCr levels were not quantitatively associated with active lesions, they may not accurately reflect the response to remission induction therapy in patients with LN.

Risk Factors for Chronic Damage Accumulation Across Different Onset Eras in Systemic Lupus Erythematosus: A Cross-sectional Analysis of a Lupus Registry of Nationwide Institutions (LUNA).

Chronic damage accumulation affects not only mortality but also quality of life in patients with systemic lupus erythematosus (SLE). Risk factors for chronic damage were explored in SLE through different onset eras. Two hundred forty-five patients at Okayama University Hospital and Showa University Hospital were divided into three groups based on the onset era: a past-onset group (onset before 1995; n=83), middle-onset group (1996-2009; n=88), and recent-onset group (after 2010; n=74). The mean Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score as an index of chronic damage was 1.93, 1.24, and 0.53 in the past-, middle-, and recent-onset groups, respectively. In the pastonset group, the total SDI score was significantly associated with glucocorticoid monotherapy by linear regression analysis (ß-coefficient [ß]=0.63; 95% confidence interval [CI], 0.21-1.05) and C-reactive protein levels (ß=0.67; 95% CI, 0.27-1.07). In the middle-onset group, the total SDI score was significantly associated with the SLE Disease Activity Index at registration (ß=0.09; 95% CI, 0.03-0.12). Reducing the accumulation of chronic damage in SLE patients might be possible with the concomitant use of immunosuppressants and tight control of disease activity.

Many-Body Chern Number without Integration.

The celebrated work of Niu, Thouless, and Wu demonstrated the quantization of Hall conductance in the presence of many-body interactions by revealing the many-body counterpart of the Chern number. The generalized Chern number is formulated in terms of the twisted angles of the boundary condition, instead of the single particle momentum, and involves an integration over all possible twisted angles. However, this formulation is physically unnatural, since topological invariants directly related to observables should be defined for each Hamiltonian under a fixed boundary condition. In this work, we show via numerical calculations that the integration is indeed unnecessary-the integrand itself is effectively quantized and the error decays exponentially with the system size. This implies that the numerical cost in computing the many-body Chern number could, in principle, be significantly reduced as it suffices to compute the Berry connection for a single value of the twisted boundary condition if the system size is sufficiently large.

Downregulation of miR-200a-3p, Targeting CtBP2 Complex, Is Involved in the Hypoproduction of IL-2 in Systemic Lupus Erythematosus-Derived T Cells.

Systemic lupus erythematosus (SLE) damages multiple organs by producing various autoantibodies. In this study, we report that decreased microRNA (miR)-200a-3p causes IL-2 hypoproduction through zinc finger E-box binding homeobox (ZEB)1 and C-terminal binding protein 2 (CtBP2) in a lupus-prone mouse. First, we performed RNA sequencing to identify candidate microRNAs and mRNAs involved in the pathogenesis of SLE. We found that miR-200a-3p was significantly downregulated, whereas its putative targets, ZEB2 and CtBP2, were upregulated in CD4+ T cells from MRL/lpr-Tnfrsf6lpr mice compared with C57BL/6J mice. ZEB1 and ZEB2 comprise the ZEB family and suppress various genes, including IL-2 by recruiting CtBP2. IL-2 plays a critical role in immune tolerance, and insufficient IL-2 production upon stimulation has been recognized in SLE pathogenesis. Therefore, we hypothesized that decreased miR-200a-3p causes IL-2 deficit through the ZEB1-CtBP2 and/or ZEB2-CtBP2 complex in SLE CD4+ T cells. Overexpression of miR-200a-3p induced IL-2 production by downregulating ZEB1, ZEB2, and CtBP2 in EL4 cell lines. We further revealed that miR-200a-3p promotes IL-2 expression by reducing the binding of suppressive ZEB1-CtBP2 and ZEB2-CtBP2 complexes on negative regulatory element A in the IL-2 promoter in EL4 cells. Interestingly, the ZEB1-CtBP2 complex on negative regulatory element A was significantly upregulated after PMA/ionomycin stimulation in lupus CD4+ T cells. Our studies have revealed a new epigenetic pathway in the control of IL-2 production in SLE whereby low levels of miR-200a-3p accumulate the binding of the ZEB1-CtBP2 complex to the IL-2 promoter and suppress IL-2 production.

Cluster Analysis Using Anti-Aminoacyl-tRNA Synthetases and SS-A/Ro52 antibodies in Patients With Polymyositis/Dermatomyositis.

OBJECTIVE: Although several autoantibodies have been identified for polymyositis/dermatomyositis (PM/DM) diagnosis, the clinical impact of these antibodies is yet to be elucidated. METHODS: Patients with PM/DM at Okayama University Hospital from 2012 to 2016 were historically enrolled, and antibody profiles were analyzed using line immunoassay. Hierarchical cluster analysis was performed based on serological analysis of anti-aminoacyl-tRNA synthetase (ARS) antibodies, including anti-Jo-1, PL-7, PL-12, EJ, OJ, and SS-A/Ro-52 antibodies. Clinical symptoms and relapse proportions were compared among these clusters. RESULTS: Sixty-one patients were enrolled in this study: 28 were diagnosed with PM, and 33 were diagnosed with DM. The following 3 clusters were determined: 1 (n = 10), anti-Jo-1 and anti-SS-A/Ro-52 antibodies double positive (10/10, 100%); 2 (n = 24), anti-SS-A/Ro-52 antibody positive (20/24, 83%), anti-Jo-1 antibody negative (24/24, 100%), and anti-ARS antibodies (excluding anti-Jo-1 antibody) positive (15/24, 63%); and 3 (n = 27), anti-Jo-1 and anti-SS-A/Ro52 antibodies double negative (26/27, 96%). The proportion of patients who relapsed was significantly lower in cluster 3 than it was in clusters 1 and 2 (risk ratio, 0.37; 95% confidence interval, 0.17-0.83; p = 0.026 and risk ratio, 0.42; 95% confidence interval, 0.20-0.89; P = 0.019, respectively). There was no difference in the proportion of relapsed patients between clusters 1 and 2. CONCLUSIONS: Our cluster analysis shows that anti-SS-A/Ro52 or any anti-ARS antibodies or both might be relevant to clinical outcomes.

Space Group Theory of Photonic Bands.

The wide-range application of photonic crystals and metamaterials benefits from the enormous design space of three-dimensional subwavelength structures. In this Letter, we study the space group constraints on photonic dispersions for all 230 space groups with time-reversal symmetry. Our theory carefully treats the unique singular point of photonic bands at zero frequency and momentum, which distinguishes photonic bands from their electronic counterpart. The results are given in terms of minimal band connectivities at zero (M) and nonzero frequencies (M^{'}). Topological band degeneracies are guaranteed to be found in space groups that do not allow band gaps between the second and third photonic bands (M>2). Our Letter provides theoretical guidelines for the choice of spatial symmetries in photonics design.

Fragile Topology and Wannier Obstructions.

Topological phases, such as Chern insulators, are defined in terms of additive indices that are stable against the addition of trivial degrees of freedom. Such topology presents an obstruction to any Wannier representation, namely, the representation of the electronic states in terms of symmetric, exponentially localized Wannier functions. Here, we address the converse question: Do obstructions to Wannier representation imply stable band topology? We answer this in the negative, pointing out that some bands can also display a distinct type of "fragile topology." Bands with fragile topology do not admit any Wannier representation by themselves, but such a representation becomes possible once certain additional trivial degrees of freedom are supplied. We construct a physical model of fragile topology on the honeycomb lattice that also helps resolve a recent puzzle in band theory. This model provides a counterexample to the assumption that splitting of an "elementary band representation" introduced in [B. Bradlyn et al., Topological quantum chemistry, Nature (London) 547, 298 (2017)] leads to bands that are individually topological. Instead, half of the split bands of our model realize a trivial band with exponentially localized symmetric Wannier functions, whereas the second half possess fragile topology. Our work highlights an important and previously overlooked connection between band structure and Wannier functions, and is expected to have far-reaching consequences given the central role played by Wannier functions in the modeling of real materials.

Universal Relation among the Many-Body Chern Number, Rotation Symmetry, and Filling.

Understanding the interplay between the topological nature and the symmetry property of interacting systems has been a central matter of condensed matter physics in recent years. In this Letter, we establish nonperturbative constraints on the quantized Hall conductance of many-body systems with arbitrary interactions. Our results allow one to readily determine the many-body Chern number modulo a certain integer without performing any integrations, solely based on the rotation eigenvalues and the average particle density of the many-body ground state.

Filling constraints for spin-orbit coupled insulators in symmorphic and nonsymmorphic crystals.

We determine conditions on the filling of electrons in a crystalline lattice to obtain the equivalent of a band insulator--a gapped insulator with neither symmetry breaking nor fractionalized excitations. We allow for strong interactions, which precludes a free particle description. Previous approaches that extend the Lieb-Schultz-Mattis argument invoked spin conservation in an essential way and cannot be applied to the physically interesting case of spin-orbit coupled systems. Here we introduce two approaches: The first one is an entanglement-based scheme, and the second one studies the system on an appropriate flat "Bieberbach" manifold to obtain the filling conditions for all 230 space groups. These approaches assume only time reversal rather than spin rotation invariance. The results depend crucially on whether the crystal symmetry is symmorphic. Our results clarify when one may infer the existence of an exotic ground state based on the absence of order, and we point out applications to experimentally realized materials. Extensions to new situations involving purely spin models are also mentioned.

Anti-SS-A/Ro antibody positivity as a risk factor for relapse in patients with polymyositis/dermatomyositis.

OBJECTIVE: The objective of this study is to elucidate predictors of relapse in patients with polymyositis and dermatomyositis (PM/DM). METHODS: Fifty PM/DM patients who achieved disease stabilization at Okayama University Hospital in 2004-2014 were enrolled retrospectively. Candidate predictors such as demographic factors, clinical symptoms, laboratory data, and treatment status were compared. RESULTS: The mean age of enrolled patients was 58 years; 34 were female. The patient groupings were as follows: 21 with PM, 27 with DM, and two with clinically amyopathic DM. During a mean observation period of 685 d, 5 patients (10%) died and 20 (40%) relapsed. The relapsed patients displayed baseline muscle weakness less frequently (85% versus 100%, p = .03) and anti-SS-A/Ro antibody more frequently (65% versus 27%, p = .007). Anti-SS-A/Ro-positive patients exhibited a higher relapse rate than anti-SS-A/Ro-negative patients (log-rank test, p = .03). Anti-SS-A/Ro-positive patients also exhibited higher anti-Jo-1 antibody positivity and lower levels of serum complement. After adjusting anti-Jo-1 antibody positivity, age, sex, CK <500 IU/L, and lung involvement, anti-SS-A/Ro positivity was still an independent risk factor for higher relapse-rate (odds ratio, 5.5; 95% confidence interval, 1.4-25.1). CONCLUSIONS: Anti-SS-A/Ro antibody positivity may be a useful biomarker for prediction of relapse.

Energy Gap of Neutral Excitations Implies Vanishing Charge Susceptibility.

In quantum many-body systems with a U(1) symmetry, such as particle number conservation and axial spin conservation, there are two distinct types of excitations: charge-neutral excitations and charged excitations. The energy gaps of these excitations may be independent from each other in strongly correlated systems. The static susceptibility of the U(1) charge vanishes when the charged excitations are all gapped, but its relation to the neutral excitations is not obvious. Here we show that a finite excitation gap of the neutral excitations is, in fact, sufficient to prove that the charge susceptibility vanishes (i.e., the system is incompressible). This result gives a partial explanation for why the celebrated quantization condition n(S-m_{z})∈Z at magnetization plateaus works even in spatial dimensions greater than one.

Lattice Homotopy Constraints on Phases of Quantum Magnets.

The Lieb-Schultz-Mattis (LSM) theorem and its extensions forbid trivial phases from arising in certain quantum magnets. Constraining infrared behavior with the ultraviolet data encoded in the microscopic lattice of spins, these theorems tie the absence of spontaneous symmetry breaking to the emergence of exotic phases like quantum spin liquids. In this work, we take a new topological perspective on these theorems, by arguing they originate from an obstruction to "trivializing" the lattice under smooth, symmetric deformations, which we call the "lattice homotopy problem." We conjecture that all LSM-like theorems for quantum magnets (many previously unknown) can be understood from lattice homotopy, which automatically incorporates the full spatial symmetry group of the lattice, including all its point-group symmetries. One consequence is that any spin-symmetric magnet with a half-integer moment on a site with even-order rotational symmetry must be a spin liquid. To substantiate the claim, we prove the conjecture in two dimensions for some physically relevant settings.

Criterion for stability of Goldstone modes and Fermi liquid behavior in a metal with broken symmetry.

There are few general physical principles that protect the low-energy excitations of a quantum phase. Of these, Goldstone's theorem and Landau-Fermi liquid theory are the most relevant to solids. We investigate the stability of the resulting gapless excitations--Nambu-Goldstone bosons (NGBs) and Landau quasiparticles--when coupled to one another, which is of direct relevance to metals with a broken continuous symmetry. Typically, the coupling between NGBs and Landau quasiparticles vanishes at low energies, leaving the gapless modes unaffected. If, however, the low-energy coupling is nonvanishing, non-Fermi liquid behavior and overdamped bosons are expected. Here we prove a general criterion that specifies when the coupling is nonvanishing. It is satisfied by the case of a nematic Fermi fluid, consistent with earlier microscopic calculations. In addition, the criterion identifies a new kind of symmetry breaking--of magnetic translations--where nonvanishing couplings should arise, opening a previously unidentified route to realizing non-Fermi liquid phases.

Alternative to Rituximab Therapy for a Patient with Ankylosing Spondylitis Who Was Unable to Continue Anti-TNF Therapy.

We herein present a case of a 38-year-old man who had bamboo spine and severe sacroiliitis and who was diagnosed with ankylosing spondylitis (AS). Infliximab (IFX) markedly improved the axial symptom but was discontinued due to the side effect of peripheral neuropathy. Switching from IFX to etanercept worsened the side effect. Rituximab (RTX) administration elicited a good response without side effects. RTX might be a suitable option for AS therapy when TNF inhibitors are difficult to use.

Prognostic factors of methotrexate-associated lymphoproliferative disorders associated with rheumatoid arthritis and plausible application of biological agents.

OBJECTIVES: To determine prognostic factors of methotrexate-associated lymphoproliferative disorder (MTX-LPD) and evaluate the efficacy and safety of biological therapy in rheumatoid arthritis (RA) complicated with MTX-LPD. METHODS: Thirty RA patients who developed MTX-LPD were investigated in this study. We compared the clinical and laboratory parameters of patients who achieved regression of LPD by MTX withdrawal with those who required chemotherapy and evaluated the clinical course of RA after LPD development. RESULTS: Twenty-three patients (76.7%) achieved regression of LPD by MTX withdrawal. Chemotherapy-free patients had a tendency of shorter RA duration (13.1 vs. 22.0 years, p = 0.108) and higher doses of MTX at LPD diagnosis (8.0 vs. 5.3 mg/w, p = 0.067) than patients who required chemotherapy. A significantly higher positive rate of peripheral blood Epstein-Barr virus (EBV)-DNA was observed in the chemotherapy-free group (9/9 vs. 0/3, p = 0.0002). Of 15 patients that received biological agents after LPD development, 14 patients (93.3%) demonstrated an improved disease activity of RA and persistent remission of LPD, whereas only one patient experienced relapse of LPD during tocilizumab therapy. CONCLUSIONS: Peripheral blood EBV-DNA positivity is a potential prognostic marker of better outcome in MTX-LPD. Biological agents could be an option for the treatment of RA patients with MTX-LPD.