Bardoxolone methyl prevents metabolic dysfunction-associated steatohepatitis by inhibiting macrophage infiltration.

BACKGROUND AND PURPOSE: Bardoxolone methyl (2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid methyl ester, CDDO-Me) is a potent activator of nuclear factor erythroid 2-related factor 2 (Nrf2), which induces the expression of antioxidative-associated genes. CDDO-Me exerts protective effects against chronic inflammatory diseases in the kidneys and lungs. However, its pharmacological effects on metabolic dysfunction-associated steatohepatitis (MASH) caused by fat accumulation remain unknown. In this study, we examined the hepatoprotective effects of CDDO-Me in a diet-induced MASH mouse model and elucidated its pharmacological mechanisms using RNA-seq analysis. EXPERIMENTAL APPROACH: CDDO-Me was orally administered to mice fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD), and histological, biochemical, and transcriptomic analyses were performed on livers of mice that developed MASH. KEY RESULTS: CDDO-Me administration induced the expression of antioxidant genes and cholesterol transporters downstream of Nrf2 and significantly prevented the symptoms of MASH. Whole-transcriptome analysis revealed that CDDO-Me inhibited the inflammatory pathway that led to phagocyte recruitment, in addition to activating the Nrf2-dependent pathway. Among inflammatory pathways, CC chemokine ligands (CCL)3 and CCL4, which are downstream of NF-κB and are associated with the recruitment of macrophages expressing CC chemokine receptors (CCR)1 and CCR5, were released into the blood in MASH mice. However, CDDO-Me directly inhibited the expression of CCL3-CCR1 and CCL4-CCR5 in macrophages. CONCLUSIONS AND IMPLICATIONS: Overall, we revealed the potent hepatoprotective effect of CDDO-Me in a MASH mouse model and demonstrated that its pharmacological effects were closely associated with a reduction of macrophage infiltration, through CCL3-CCR1 and CCL4-CCR5 inhibition, in addition to Nrf2-mediated hepatoprotective effects.

Hybrid Moiré Excitons and Trions in Twisted MoTe2-MoSe2 Heterobilayers.

We report experimental and theoretical studies of MoTe2-MoSe2 heterobilayers with rigid moiré superlattices controlled by the twist angle. Using an effective continuum model that combines resonant interlayer electron tunneling with stacking-dependent moiré potentials, we identify the nature of moiré excitons and the dependence of their energies, oscillator strengths, and Landé g-factors on the twist angle. Within the same framework, we interpret distinct signatures of bound complexes among electrons and moiré excitons in nearly collinear heterostacks. Our work provides a fundamental understanding of hybrid moiré excitons and trions in MoTe2-MoSe2 heterobilayers and establishes the material system as a prime candidate for optical studies of correlated phenomena in moiré lattices.

Ferrielectricity controlled widely-tunable magnetoelectric coupling in van der Waals multiferroics.

The discovery of various primary ferroic phases in atomically-thin van der Waals crystals have created a new two-dimensional wonderland for exploring and manipulating exotic quantum phases. It may also bring technical breakthroughs in device applications, as evident by prototypical functionalities of giant tunneling magnetoresistance, gate-tunable ferromagnetism and non-volatile ferroelectric memory etc. However, two-dimensional multiferroics with effective magnetoelectric coupling, which ultimately decides the future of multiferroic-based information technology, has not been realized yet. Here, we show that an unconventional magnetoelectric coupling mechanism interlocked with heterogeneous ferrielectric transitions emerges at the two-dimensional limit in van der Waals multiferroic CuCrP2S6 with inherent antiferromagnetism and antiferroelectricity. Distinct from the homogeneous antiferroelectric bulk, thin-layer CuCrP2S6 under external electric field makes layer-dependent heterogeneous ferrielectric transitions, minimizing the depolarization effect introduced by the rearrangements of Cu+ ions within the ferromagnetic van der Waals cages of CrS6 and P2S6 octahedrons. The resulting ferrielectric phases are characterized by substantially reduced interlayer magnetic coupling energy of nearly 50% with a moderate electric field of 0.3 V nm-1, producing widely-tunable magnetoelectric coupling which can be further engineered by asymmetrical electrode work functions.

Conduction Band Replicas in a 2D Moiré Semiconductor Heterobilayer.

Stacking monolayer semiconductors creates moiré patterns, leading to correlated and topological electronic phenomena, but measurements of the electronic structure underpinning these phenomena are scarce. Here, we investigate the properties of the conduction band in moiré heterobilayers of WS2/WSe2 using submicrometer angle-resolved photoemission spectroscopy with electrostatic gating. We find that at all twist angles the conduction band edge is the K-point valley of the WS2, with a band gap of 1.58 ± 0.03 eV. From the resolved conduction band dispersion, we deduce an effective mass of 0.15 ± 0.02 me. Additionally, we observe replicas of the conduction band displaced by reciprocal lattice vectors of the moiré superlattice. We argue that the replicas result from the moiré potential modifying the conduction band states rather than final-state diffraction. Interestingly, the replicas display an intensity pattern with reduced 3-fold symmetry, which we show implicates the pseudo vector potential associated with in-plane strain in moiré band formation.

Oscillating paramagnetic Meissner effect and Berezinskii-Kosterlitz-Thouless transition in underdoped Bi2Sr2CaCu2O8+δ.

Superconducting phase transitions in two dimensions lie beyond the description of the Ginzburg-Landau symmetry-breaking paradigm for three-dimensional superconductors. They are Berezinskii-Kosterlitz-Thouless (BKT) transitions of paired-electron condensate driven by the unbinding of topological excitations, i.e. vortices. The recently discovered monolayers of layered high-transition-temperature ([Formula: see text]) cuprate superconductor Bi2Sr2CaCu2O8+δ (Bi2212) meant that this 2D superconductor promised to be ideal for the study of unconventional superconductivity. But inhomogeneity posed challenges for distinguishing BKT physics from charge correlations in this material. Here, we utilize the phase sensitivity of scanning superconducting quantum interference device microscopy susceptometry to image the local magnetic response of underdoped Bi2212 from the monolayer to the bulk throughout its phase transition. The monolayer segregates into domains with independent phases at elevated temperatures below [Formula: see text]. Within a single domain, we find that the susceptibility oscillates with flux between diamagnetism and paramagnetism in a Fraunhofer-like pattern up to [Formula: see text]. The finite modulation period, as well as the broadening of the peaks when approaching [Formula: see text] from below, suggests well-defined vortices that are increasingly screened by the dissociation of vortex-antivortex plasma through a BKT transition. In the multilayers, the susceptibility oscillation differs in a small temperature regime below [Formula: see text], consistent with a dimensional crossover led by interlayer coupling. Serving as strong evidence for BKT transition in the bulk, we observe a sharp jump in phase stiffness and paramagnetism at small fields just below [Formula: see text]. These results unify the superconducting phase transitions from the monolayer to the bulk underdoped Bi2212, and can be collectively referred to as the BKT transition with interlayer coupling.

Two-Dimensional Moiré Polaronic Electron Crystals.

Two-dimensional moiré materials have emerged as the most versatile platform for realizing quantum phases of electrons. Here, we explore the stability origins of correlated states in WSe_{2}/WS_{2} moiré superlattices. We find that ultrafast electronic excitation leads to partial melting of the Mott states on timescales 5 times longer than predictions from the charge hopping integrals and that the melting rates are thermally activated, with activation energies of 18±3 and 13±2 meV for the one- and two-hole Mott states, respectively, suggesting significant electron-phonon coupling. A density functional theory calculation of the one-hole Mott state confirms polaron formation and yields a hole-polaron binding energy of 16 meV. These findings reveal a close interplay of electron-electron and electron-phonon interactions in stabilizing the polaronic Mott insulators at transition metal dichalcogenide moiré interfaces.

Lymphovascular invasion is associated with poor long-term outcomes in patients with pT1N0-3 or pT2-3N0 remnant gastric cancer: a retrospective cohort study.

BACKGROUND: Lymphovascular invasion (LVI) is a poor prognostic factor in various malignancies. However, its prognostic effect in remnant gastric cancer (RGC) remains unclear. We examined the correlation between LVI and disease prognosis in patients with T1N0-3 or T2-3N0 RGC in whom adjuvant chemotherapy was not indicated and a treatment strategy was not established. METHODS: We retrospectively analyzed patients with T1N0-3 and T2-3N0 RGC who underwent curative surgery at the Kyoto Prefectural University of Medicine between 1997 and 2019 and at the Kyoto Chubu Medical Center between 2009 and 2019. RESULTS: Fifteen of 38 patients (39.5%) with RGC were positive for LVI. Patients with LVI had a significantly poorer prognosis for both overall survival ([OS]: P = 0.006) and recurrence-free survival ([RFS]: P = 0.001) than those without LVI. Multivariate analyses using the Cox proportional hazards model revealed LVI as an independent prognostic factor affecting OS (P = 0.024; hazard ratio 8.27, 95% confidence interval:1.285-161.6) and RFS (P = 0.013; hazard ratio 8.98, 95% confidence interval:1.513-171.2). CONCLUSIONS: LVI is a prognostic factor for patients with T1N0-3 or T2-3N0 RGC. Evaluating LVI may be useful for determining treatment strategies for RGC.

Probing the tunable multi-cone band structure in Bernal bilayer graphene.

Bernal bilayer graphene (BLG) offers a highly flexible platform for tuning the band structure, featuring two distinct regimes. One is a tunable band gap induced by large displacement fields. Another is a gapless metallic band occurring at low fields, featuring rich fine structure consisting of four linearly dispersing Dirac cones and van Hove singularities. Even though BLG has been extensively studied experimentally, the evidence of this band structure is still elusive, likely due to insufficient energy resolution. Here, we use Landau levels as markers of the energy dispersion and analyze the Landau level spectrum in a regime where the cyclotron orbits of electrons or holes in momentum space are small enough to resolve the distinct mini Dirac cones. We identify the presence of four Dirac cones and map out topological transitions induced by displacement field. By clarifying the low-energy properties of BLG bands, these findings provide a valuable addition to the toolkit for graphene electronics.

Link between T-Linear Resistivity and Quantum Criticality in Ambipolar Black Phosphorus.

The interplay between strong Coulomb interactions and kinetic energy leads to intricate many-body competing ground states owing to quantum fluctuations in 2D electron and hole gases. However, the simultaneous observation of quantum critical phenomena in both electron and hole regimes remains elusive. Here, we utilize anisotropic black phosphorus (BP) to show density-driven metal-insulator transition with a critical conductance ∼e2/h which highlights the significant role of quantum fluctuations in both hole and electron regimes. We observe a T-linear resistivity from the deep metallic phase to the metal-insulator boundary at moderate temperatures, while it turns to Fermi liquid behavior in the deep metallic phase at low temperatures in both regimes. An analysis of the resistivity suggests that disorder-dominated transport leads to T-linear behavior in the hole regime, while in the electron regime, the T-linear resistivity results from strong Coulomb interactions, suggestive of strange-metal behavior. Successful scaling collapse of the resistivity in the T-linear region demonstrates the link between quantum criticality and the T-linear resistivity in both regimes. Our study provides compelling evidence that ambipolar BP could serve as an exciting testbed for investigating exotic states and quantum critical phenomena in hole and electron regimes of 2D semiconductors.

Impact of Spin-Entropy on the Thermoelectric Properties of a 2D Magnet.

Heat-to-charge conversion efficiency of thermoelectric materials is closely linked to the entropy per charge carrier. Thus, magnetic materials are promising building blocks for highly efficient energy harvesters as their carrier entropy is boosted by a spin degree of freedom. In this work, we investigate how this spin-entropy impacts heat-to-charge conversion in the A-type antiferromagnet CrSBr. We perform simultaneous measurements of electrical conductance and thermocurrent while changing magnetic order using the temperature and magnetic field as tuning parameters. We find a strong enhancement of the thermoelectric power factor at around the Néel temperature. We further reveal that the power factor at low temperatures can be increased by up to 600% upon applying a magnetic field. Our results demonstrate that the thermoelectric properties of 2D magnets can be optimized by exploiting the sizable impact of spin-entropy and confirm thermoelectric measurements as a sensitive tool to investigate subtle magnetic phase transitions in low-dimensional magnets.

Elementary excitations of single-photon emitters in hexagonal boron nitride.

Single-photon emitters serve as building blocks for many emerging concepts in quantum photonics. The recent identification of bright, tunable and stable emitters in hexagonal boron nitride (hBN) has opened the door to quantum platforms operating across the infrared to ultraviolet spectrum. Although it is widely acknowledged that defects are responsible for single-photon emitters in hBN, crucial details regarding their origin, electronic levels and orbital involvement remain unknown. Here we employ a combination of resonant inelastic X-ray scattering and photoluminescence spectroscopy in defective hBN, unveiling an elementary excitation at 285 meV that gives rise to a plethora of harmonics correlated with single-photon emitters. We discuss the importance of N π* anti-bonding orbitals in shaping the electronic states of the emitters. The discovery of elementary excitations in hBN provides fundamental insights into quantum emission in low-dimensional materials, paving the way for future investigations in other platforms.

Linear resistivity at van Hove singularities in twisted bilayer WSe2.

Different mechanisms driving a linear temperature dependence of the resistivity ρ ∼ T at van Hove singularities (VHSs) or metal-insulator transitions when doping a Mott insulator are being debated intensively with competing theoretical proposals. We experimentally investigate this using the exceptional tunability of twisted bilayer (TB) WSe2 by tracking the parameter regions where linear-in-T resistivity is found in dependency of displacement fields, filling, and magnetic fields. We find that even when the VHSs are tuned rather far away from the half-filling point and the Mott insulating transition is absent, the T-linear resistivity persists at the VHSs. When doping away from the VHSs, the T-linear behavior quickly transitions into a Fermi liquid behavior with a T2 relation. No apparent dependency of the linear-in-T resistivity, besides a rather strong change of prefactor, is found when applying displacement fields as long as the filling is tuned to the VHSs, including D ∼ 0.28 V/nm where a high-order VHS is expected. Intriguingly, such non-Fermi liquid linear-in-T resistivity persists even when magnetic fields break the spin-degeneracy of the VHSs at which point two linear in T regions emerge, for each of the split VHSs separately. This points to a mechanism of enhanced scattering at generic VHSs rather than only at high-order VHSs or by a quantum critical point during a Mott transition. Our findings provide insights into the many-body consequences arising out of VHSs, especially the non-Fermi liquid behavior found in moiré materials.

Cathodoluminescence emission and electron energy loss absorption from a 2D transition metal dichalcogenide in van der Waals heterostructures.

Nanoscale variations of optical properties in transition metal dichalcogenide (TMD) monolayers can be explored with cathodoluminescence (CL) and electron energy loss spectroscopy (EELS) using electron microscopes. To increase the CL emission intensity from TMD monolayers, the MoSe2flakes are encapsulated in hexagonal boron nitride (hBN), creating van der Waals (VdW) heterostructures. Until now, the studies have been exclusively focused on scanning transmission electron microscopy (STEM-CL) or scanning electron microscopy (SEM-CL), separately. Here, we present results, using both techniques on the same sample, thereby exploring a large acceleration voltage range. We correlate the CL measurements with STEM-EELS measurements acquired with different energy dispersions, to access both the low-loss region at ultra-high spectral resolution, and the core-loss region. This provides information about the weight of the various absorption phenomena including the direct TMD absorption, the hBN interband transitions, the hBN bulk plasmon, and the core losses of the atoms present in the heterostructure. The S(T)EM-CL measurements from the TMD monolayer only show emission from the A exciton. Combining the STEM-EELS and S(T)EM-CL measurements, we can reconstruct different decay pathways leading to the A exciton CL emission. The comparison with SEM-CL shows that this is also a good technique for TMD heterostructure characterization, where the reduced demands on sample preparation are appealing. To demonstrate the capabilities of SEM-CL imaging, we also measured on a SiO2/Si substrate, quintessential in the sample preparation of two-dimensional materials, which is electron-opaque and can only be measured in SEM-CL. The CL-emitting defects of SiO2make this substrate challenging to use, but we demonstrate that this background can be suppressed by using lower electron energy.

Near-field coupling of interlayer excitons in MoSe2/WSe2 heterobilayers to surface plasmon polaritons.

Two-dimensional (2D) transition metal dichalcogenides have emerged as promising quantum functional blocks benefitting from their unique combination of spin, valley, and layer degrees of freedom, particularly for the tremendous flexibility of moiré superlattices formed by van der Waals stacking. These degrees of freedom coupled with the enhanced Coulomb interaction in 2D structures allow excitons to serve as on-chip information carriers. However, excitons are spatially circumscribed due to their low mobility and limited lifetime. One way to overcome these limitations is through the coupling of excitons with surface plasmon polaritons (SPPs), which facilitates an interaction between remote quantum states. Here, we showcase the successful coupling of SPPs with interlayer excitons in molybdenum diselenide/tungsten diselenide heterobilayers. Our results indicate that the valley polarization can be efficiently transferred to SPPs, enabling preservation of polarization information even after propagating tens of micrometers.

Stark Effects of Rydberg Excitons in a Monolayer WSe2 P-N Junction.

The enhanced Coulomb interaction in two-dimensional semiconductors leads to tightly bound electron-hole pairs known as excitons. The large binding energy of excitons enables the formation of Rydberg excitons with high principal quantum numbers (n), analogous to Rydberg atoms. Rydberg excitons possess strong interactions among themselves as well as sensitive responses to external stimuli. Here, we probe Rydberg exciton resonances through photocurrent spectroscopy in a monolayer WSe2 p-n junction formed by a split-gate geometry. We show that an external in-plane electric field not only induces a large Stark shift of Rydberg excitons up to quantum principal number 3 but also mixes different orbitals and brightens otherwise dark states such as 3p and 3d. Our study provides an exciting platform for engineering Rydberg excitons for new quantum states and quantum sensing.

Direct observation of a magnetic-field-induced Wigner crystal.

Wigner predicted that when the Coulomb interactions between electrons become much stronger than their kinetic energy, electrons crystallize into a closely packed lattice1. A variety of two-dimensional systems have shown evidence for Wigner crystals2-11 (WCs). However, a spontaneously formed classical or quantum WC has never been directly visualized. Neither the identification of the WC symmetry nor direct investigation of its melting has been accomplished. Here we use high-resolution scanning tunnelling microscopy measurements to directly image a magnetic-field-induced electron WC in Bernal-stacked bilayer graphene and examine its structural properties as a function of electron density, magnetic field and temperature. At high fields and the lowest temperature, we observe a triangular lattice electron WC in the lowest Landau level. The WC possesses the expected lattice constant and is robust between filling factor ν ≈ 0.13 and ν ≈ 0.38 except near fillings where it competes with fractional quantum Hall states. Increasing the density or temperature results in the melting of the WC into a liquid phase that is isotropic but has a modulated structure characterized by the Bragg wavevector of the WC. At low magnetic fields, the WC unexpectedly transitions into an anisotropic stripe phase, which has been commonly anticipated to form in higher Landau levels. Analysis of individual lattice sites shows signatures that may be related to the quantum zero-point motion of electrons in the WC lattice.

Correlation-driven nonequilibrium exciton site transition in a WSe2/WS2 moiré supercell.

Moiré superlattices of transition metal dichalcogenides offer a unique platform to explore correlated exciton physics with optical spectroscopy. Whereas the spatially modulated potentials evoke that the exciton resonances are distinct depending on a site in a moiré supercell, there have been no clear demonstration how the moiré excitons trapped in different sites dynamically interact with the doped carriers; so far the exciton-electron dynamic interactions were presumed to be site-dependent. Thus, the transient emergence of nonequilibrium correlations are open questions, but existing studies are limited to steady-state optical measurements. Here we report experimental fingerprints of site-dependent exciton correlations under continuous-wave as well as ultrashort optical excitations. In near-zero angle-aligned WSe2/WS2 heterobilayers, we observe intriguing polarization switching and strongly enhanced Pauli blocking near the Mott insulating state, dictating the dominant correlation-driven effects. When the twist angle is near 60°, no such correlations are observed, suggesting the strong dependence of atomic registry in moiré supercell configuration. Our studies open the door to largely unexplored nonequilibrium correlations of excitons in moiré superlattices.

Evolution of the flat band and the role of lattice relaxations in twisted bilayer graphene.

Magic-angle twisted bilayer graphene exhibits correlated phenomena such as superconductivity and Mott insulating states related to the weakly dispersing flat band near the Fermi energy. Such a flat band is expected to be sensitive to both the moiré period and lattice relaxations. Thus, clarifying the evolution of the electronic structure with the twist angle is critical for understanding the physics of magic-angle twisted bilayer graphene. Here we combine nano-spot angle-resolved photoemission spectroscopy and atomic force microscopy to resolve the fine electronic structure of the flat band and remote bands, as well as their evolution with twist angle from 1.07° to 2.60°. Near the magic angle, the dispersion is characterized by a flat band near the Fermi energy with a strongly reduced band width. Moreover, we observe a spectral weight transfer between remote bands at higher binding energy, which allows to extract the modulated interlayer spacing near the magic angle. Our work provides direct spectroscopic information on flat band physics and highlights the important role of lattice relaxations.

Real-world efficacy and safety of tofacitinib treatment in Asian patients with ulcerative colitis.

BACKGROUND: Real-world data on tofacitinib (TOF) covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis (UC) are scarce. AIM: To investigate the long-term efficacy and safety of TOF treatment for UC, including clinical issues. METHODS: We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease center. All consecutive UC patients who received TOF between May 2018 and February 2020 were enrolled. Patients were followed up until August 2020. The primary outcome was the clinical response rate at week 8. Secondary outcomes included clinical remission at week 8, cumulative persistence rate of TOF administration, colectomy-free survival, relapse after tapering of TOF and predictors of clinical response at week 8 and week 48. RESULTS: The clinical response and remission rates were 66.3% and 50.5% at week 8, and 47.1% and 43.5% at week 48, respectively. The overall cumulative clinical remission rate was 61.7% at week 48 and history of anti-tumor necrosis factor-alpha (TNF-α) agents use had no influence (P = 0.25). The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8 (30.9% vs 88.1%; P < 0.001). Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8 (odds ratio: 0.61, 95% confidence interval: 0.45-0.82, P = 0.001). Relapse occurred in 45.7% of patients after TOF tapering, and 85.7% of patients responded within 4 wk after re-increase. All 6 patients with herpes zoster (HZ) developed the infection after achieving remission by TOF. CONCLUSION: TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-α agents. Most relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off TOF. Special attention is needed for tapering and HZ.

High-Mobility Compensated Semimetals, Orbital Magnetization, and Umklapp Scattering in Bilayer Graphene Moiré Superlattices.

Twist-controlled moiré superlattices (MSs) have emerged as a versatile platform for realizing artificial systems with complex electronic spectra. The combination of Bernal-stacked bilayer graphene (BLG) and hexagonal boron nitride (hBN) can give rise to an interesting MS, which has recently featured a set of unexpected behaviors, such as unconventional ferroelectricity and the electronic ratchet effect. Yet, the understanding of the electronic properties of BLG/hBN MS has, at present, remained fairly limited. Here, we combine magneto-transport and low-energy sub-THz excitation to gain insights into the properties of this MS. We demonstrate that the alignment between BLG and hBN crystal lattices results in the emergence of compensated semimetals at some integer fillings of the moiré bands, separated by van Hove singularities where the Lifshitz transition occurs. A particularly pronounced semimetal develops when eight holes reside in the moiré unit cell, where coexisting high-mobility electron and hole systems feature strong magnetoresistance reaching 2350% already at B = 0.25 T. Next, by measuring the THz-driven Nernst effect in remote bands, we observe valley splitting, indicating an orbital magnetization characterized by a strongly enhanced effective gv-factor of 340. Finally, using THz photoresistance measurements, we show that the high-temperature conductivity of the BLG/hBN MS is limited by electron-electron umklapp processes. Our multifaceted analysis introduces THz-driven magnetotransport as a convenient tool to probe the band structure and interaction effects in van der Waals materials and provides a comprehensive understanding of the BLG/hBN MS.