G protein-coupled receptor kinase 2 as a novel therapeutic target for gland fibrosis of Sjögren's syndrome.

Sjogren's syndrome (SS) is a chronic, progressive autoimmune disorder characterized by gland fibrosis. We previously found a close correlation between gland fibrosis and the expression of G protein-coupled receptor kinase 2 (GRK2). In this study we explored the pathological and therapeutic significance of GRK2 in SS. Submandibular gland (SMG) antigen-induced SS mouse model was established in WT and GRK2+/- mice. We showed that the expression levels of GRK2 were significantly up-regulated in glandular tissue and positively correlated with fibrotic morphology in SS patients and mice. Hemizygous knockout of GRK2 significantly inhibited the gland fibrosis. In mouse salivary gland epithelial cells (SGECs), we demonstrated that GRK2 interacted with Smad2/3 to positively regulate the activation of TGF-ß-Smad signaling with a TGF-ß-GRK2 positive feedback loop contributing to gland fibrosis. Hemizygous knockout of GRK2 attenuated TGF-ß-induced collagen I production in SGECs in vitro and hindered gland fibrosis in murine SS though preventing Smad2/3 nuclear translocation. Around 28 days post immunization with SMG antigen, WT SS mice were treated with a specific GRK2 inhibitor paroxetine (Par, 5 mg·kg-1·d-1, i.g. for 19 days). We found that Par administration significantly attenuated gland fibrosis and alleviated the progression of SS in mice. We conclude that genetic knockdown or pharmacological inhibition of GRK2 significantly attenuates gland fibrosis and alleviates the progression of SS. GRK2 binds to Smad2/3 and positively regulates the activation of TGF-ß-Smad signaling. A TGF-ß-GRK2 positive feedback loop contributes to gland fibrosis. Our research points out that GRK2 could be a promising therapeutic target for treating SS.

Realization of exceptional points along a synthetic orbital angular momentum dimension.

Exceptional points (EPs), at which more than one eigenvalue and eigenvector coalesce, are unique spectral features of non-Hermiticity (NH) systems. They exist widely in open systems with complex energy spectra. We experimentally demonstrate the appearance of paired EPs in a periodical-driven degenerate optical cavity along the synthetic orbital angular momentum dimension with a tunable parameter. The complex-energy band structures and the key features of EPs, i.e., their bulk Fermi arcs, parity-time symmetry breaking transition, energy swapping, and half-integer band windings, are directly observed by detecting the wavefront angle-resolved transmission spectrum. Our results demonstrate the flexibility of using the photonic synthetic dimensions to implement NH systems beyond their geometric dimension and EP-based sensing.

Topological band structure via twisted photons in a degenerate cavity.

Synthetic dimensions based on particles' internal degrees of freedom, such as frequency, spatial modes and arrival time, have attracted significant attention. They offer ideal large-scale lattices to simulate nontrivial topological phenomena. Exploring more synthetic dimensions is one of the paths toward higher dimensional physics. In this work, we design and experimentally control the coupling among synthetic dimensions consisting of the intrinsic photonic orbital angular momentum and spin angular momentum degrees of freedom in a degenerate optical resonant cavity, which generates a periodically driven spin-orbital coupling system. We directly characterize the system's properties, including the density of states, energy band structures and topological windings, through the transmission intensity measurements. Our work demonstrates a mechanism for exploring the spatial modes of twisted photons as the synthetic dimension, which paves the way to design rich topological physics in a highly compact platform.

Simulating electrical fields in the orbital angular momentum space of light.

We study a system of coupled degenerate cavities with a switchable beam rotator embedded in the optical path of the main cavity. By exploiting the phase shift of the beam rotator dependent on the orbital angular momentum of the optical modes, and modulating the phase imbalance in the auxiliary cavity, it is shown that the system dynamics is equivalent to that of a charged particle in a 1D lattice subject to both static and time-dependent electrical fields. We investigate interesting physics and phenomena such as Bloch oscillations that arise due to the simulated electrical fields, and discuss how they can be used for practical purposes such as storing optical signals in a quantum memory. We also present a powerful measurement scheme to detect the system dynamics that is non-intrusive and technically easy to perform.

TNF-α impairs EP4 signaling through the association of TRAF2-GRK2 in primary fibroblast-like synoviocytes.

Our previous study showed that chronic treatment with tumor necrosis factor-α (TNF-α) decreased cAMP concentration in fibroblast-like synoviocytes (FLSs) of collagen-induced arthritis (CIA) rats. In this study we investigated how TNF-α impairs cAMP homeostasis, particularly clarifying the potential downstream molecules of TNF-α and prostaglandin receptor 4 (EP4) signaling that would interact with each other. Using a cAMP FRET biosensor PM-ICUE3, we demonstrated that TNF-α (20 ng/mL) blocked ONO-4819-triggered EP4 signaling, but not Butaprost-triggered EP2 signaling in normal rat FLSs. We showed that TNF-α (0.02-20 ng/mL) dose-dependently reduced EP4 membrane distribution in normal rat FLS. TNF-α significantly increased TNF receptor 2 (TNFR2) expression and stimulated proliferation in human FLS (hFLS) via ecruiting TNF receptor-associated factor 2 (TRAF2) to cell membrane. More interestingly, we revealed that TRAF2 interacted with G protein-coupled receptor kinase (GRK2) in the cytoplasm of primary hFLS and helped to bring GRK2 to cell membrane in response of TNF-α stimulation, the complex of TRAF2 and GRK2 then separated on the membrane, and translocated GRK2 induced the desensitization and internalization of EP4, leading to reduced production of intracellular cAMP. Silencing of TRAF2 by siRNA substantially diminished TRAF2-GRK2 interaction, blocked the translocation of GRK2, and resulted in upregulated expression of membrane EP4 and intracellular cAMP. In CIA rats, administration of paroxetine to inhibit GRK2 effectively improved the symptoms and clinic parameters with significantly reduced joint synovium inflammation and bone destruction. These results elucidate a novel form of cross-talk between TNFR (a cytokine receptor) and EP4 (a typical G protein-coupled receptor) signaling pathways. The interaction between TRAF2 and GRK2 may become a potential new drug target for the treatment of inflammatory diseases.

Deficiency of ß-arrestin2 exacerbates inflammatory arthritis by facilitating plasma cell formation.

ß-arrestin2 (ß-arr2) is, a key protein that mediates desensitization and internalization of G protein-coupled receptors and participates in inflammatory and immune responses. Deficiency of ß-arr2 has been found to exacerbate collagen antibody-induced arthritis (CAIA) through unclear mechanisms. In this study we tried to elucidate the molecular mechanisms underlying ß-arr2 depletion-induced exacerbation of CAIA. CAIA was induced in ß-arr2-/- and wild-type (WT) mice by injection of collagen antibodies and LPS. The mice were sacrificed on d 13 after the injection, spleen, thymus and left ankle joints were collected for analysis. Arthritis index (AI) was evaluated every day or every 2 days. We showed that ß-arr2-/- mice with CAIA had a further increase in the percentage of plasma cells in spleen as compared with WT mice with CAIA, which was in accordance with elevated serum IgG1 and IgG2A expression and aggravating clinical performances, pathologic changes in joints and spleen, joint effusion, and joint blood flow. Both LPS stimulation of isolated B lymphocytes in vitro and TNP-LPS challenge in vivo led to significantly higher plasma cell formation and antibodies production in ß-arr2-/- mice as compared with WT mice. LPS treatment induced membrane distribution of toll-like receptor 4 (TLR4) on B lymphocytes, accordingly promoted the nuclear translocation of NF-κB and the transcription of Blimp1. Immunofluorescence analysis confirmed that more TLR4 colocalized with ß-arr2 in B lymphocytes in response to LPS stimulation. Depletion of ß-arr2 restrained TLR4 on B lymphocyte membrane after LPS treatment and further enhanced downstream NF-κB signaling leading to additional increment in plasma cell formation. In summary, ß-arr2 depletion exacerbates CAIA and further increases plasma cell differentiation and antibody production through inhibiting TLR4 endocytosis and aggravating NF-κB signaling.

Flexible degenerate cavity with ellipsoidal mirrors.

Here we present a design of a traveling-wave optical cavity containing four identical ellipsoidal mirrors arranged in a square. The cavity proves to support more than 21 Laguerre-Gaussian modes simultaneously. There is a polarization splitting in the cavity that can be used for polarization filtering with a high isolation level.

Experimental demonstration of suppressing residual geometric dephasing.

The geometric phase is regarded as a promising strategy in fault tolerance quantum information processing (QIP) domain due to its phase only depending on the geometry of the path executed. However, decoherence caused by environmental noise will destroy the geometric phase. Traditional dynamic decoupling sequences can eliminate dynamic dephasing but can not reduce residual geometric dephasing, which is still vital for high-precision quantum manipulation. In this work, we experimentally demonstrate effective suppression of residual geometric dephasing with modified dynamic decoupling schemes, using a single trapped 171Yb+ ion. The experimental results show that the modified schemes can reduce dephasing rate up to more than one order of magnitude compared with traditional dynamic decoupling schemes, where residual geometric dephasing dominates. Besides, we also investigate the impact of intensity and correlation time of the low-frequency noise on coherence of the quantum system. And we confirm these methods can be used in many cases.

Synthetic Landau Levels and Spinor Vortex Matter on a Haldane Spherical Surface with a Magnetic Monopole.

We present a flexible scheme to realize exact flat Landau levels on curved spherical geometry in a system of spinful cold atoms. This is achieved by applying the Floquet engineering of a magnetic quadrupole field to create a synthetic monopole field in real space. The system can be exactly mapped to the electron-monopole system on a sphere, thus realizing Haldane's spherical geometry for fractional quantum Hall physics. This method works for either bosons or fermions. We investigate the ground-state vortex pattern for an s-wave interacting atomic condensate by mapping this system to the classical Thompson's problem. The distortion and stability of the vortex pattern are further studied in the presence of dipolar interaction. Our scheme is compatible with the current experimental setup, and may serve as a promising route of investigating quantum Hall physics and exotic spinor vortex matter on curved space.

Elaborate synthesis of black tin oxide-black titanium oxide core-shell nanotubes for ultrastable and fast lithium storage.

Herein, we report on the elaborate synthesis of a novel hybrid architecture, i.e., black tin oxide-black titanium oxide core-shell nanotubes (denoted as TiO2-x@SnO2-x nanotubes) by NaBH4 co-reduction. The synergistic interplay between the SnO2-x core and the TiO2-x shell results in superior cyclability and rate capability for ultrastable and fast lithium storage.

Synthetic-lattice enabled all-optical devices based on orbital angular momentum of light.

All-optical photonic devices are crucial for many important photonic technologies and applications, ranging from optical communication to quantum information processing. Conventional design of all-optical devices is based on photon propagation and interference in real space, which may rely on large numbers of optical elements, and the requirement of precise control makes this approach challenging. Here we propose an unconventional route for engineering all-optical devices using the photon's internal degrees of freedom, which form photonic crystals in such synthetic dimensions for photon propagation and interference. We demonstrate this design concept by showing how important optical devices such as quantum memory and optical filters can be realized using synthetic orbital angular momentum (OAM) lattices in degenerate cavities. The design route utilizing synthetic photonic lattices may significantly reduce the requirement for numerous optical elements and their fine tuning in conventional design, paving the way for realistic all-optical photonic devices with novel functionalities.

Degenerate cavity supporting more than 31 Laguerre-Gaussian modes.

Photons propagating in Laguerre-Gaussian modes have characteristic orbital angular momenta, which are fundamental optical degrees of freedom. The orbital angular momentum of light has potential application in high-capacity optical communication and even in quantum information processing. In this work, we experimentally construct a ring cavity with four lenses and four mirrors that is completely degenerate for Laguerre-Gaussian modes. By measuring the transmitted peaks and patterns of different modes, the ring cavity is shown to support more than 31 Laguerre-Gaussian modes. The constructed degenerate cavity opens a new way for using the unlimited resource of available angular momentum states simultaneously.

Cavity-Assisted Single-Mode and Two-Mode Spin-Squeezed States via Phase-Locked Atom-Photon Coupling.

We propose a scheme to realize the two-axis countertwisting spin-squeezing Hamiltonian inside an optical cavity with the aid of phase-locked atom-photon coupling. By careful analysis and extensive simulation, we demonstrate that our scheme is robust against dissipation caused by cavity loss and atomic spontaneous emission, and it can achieve significantly higher squeezing than one-axis twisting. We further show how our idea can be extended to generate two-mode spin-squeezed states in two coupled cavities. Because of its easy implementation and high tunability, our scheme is experimentally realizable with current technologies.

Dynamically Manipulating Topological Physics and Edge Modes in a Single Degenerate Optical Cavity.

We propose a scheme to simulate topological physics within a single degenerate cavity, whose modes are mapped to lattice sites. A crucial ingredient of the scheme is to construct a sharp boundary so that the open boundary condition can be implemented for this effective lattice system. In doing so, the topological properties of the system can manifest themselves on the edge states, which can be probed from the spectrum of an output cavity field. We demonstrate this with two examples: a static Su-Schrieffer-Heeger chain and a periodically driven Floquet topological insulator. Our work opens up new avenues to explore exotic photonic topological phases inside a single optical cavity.

Aluminothermic reduction enabled synthesis of silicon hollow microspheres from commercialized silica nanoparticles for superior lithium storage.

We report the aluminothermic reduction enabled synthesis of silicon hollow microspheres from commercialized silica nanoparticles by controlled transformation and organization. The synergistically integrated merits of a simple process and delicate structural design lay a basis for developing an industrially viable silicon anode with optimized electrochemical performances.

Constructing Novel Si@SnO2 Core-Shell Heterostructures by Facile Self-Assembly of SnO2 Nanowires on Silicon Hollow Nanospheres for Large, Reversible Lithium Storage.

Developing an industrially viable silicon anode, featured by the highest theoretical capacity (4200 mA h g(-1)) among common electrode materials, is still a huge challenge because of its large volume expansion during repeated lithiation-delithiation as well as low intrinsic conductivity. Here, we expect to address these inherent deficiencies simultaneously with an interesting hybridization design. A facile self-assembly approach is proposed to decorate silicon hollow nanospheres with SnO2 nanowires. The two building blocks, hand in hand, play a wonderful duet by bridging their appealing functionalities in a complementary way: (1) The silicon hollow nanospheres, in addition to the major role as a superior capacity contributor, also act as a host material (core) to partially accommodate the volume expansion, thus alleviating the capacity fading by providing abundant hollow interiors, void spaces, and surface areas. (2) The SnO2 nanowires serve as a conductive coating (shell) to enable efficient electron transport due to a relatively high conductivity, thereby improving the cyclability of silicon. Compared to other conductive dopants, the SnO2 nanowires with a high theoretical capacity (790 mA h g(-1)) can contribute outstanding electrochemical reaction kinetics, further adding value to the ultimate electrochemical performances. The resulting novel Si@SnO2 core-shell heterostructures exhibit remarkable synergy in large, reversible lithium storage, delivering a reversible capacity as high as 1869 mA h g(-1)@500 mA g(-1) after 100 charging-discharging cycles.

Quantum simulation of 2D topological physics in a 1D array of optical cavities.

Orbital angular momentum of light is a fundamental optical degree of freedom characterized by unlimited number of available angular momentum states. Although this unique property has proved invaluable in diverse recent studies ranging from optical communication to quantum information, it has not been considered useful or even relevant for simulating nontrivial physics problems such as topological phenomena. Contrary to this misconception, we demonstrate the incredible value of orbital angular momentum of light for quantum simulation by showing theoretically how it allows to study a variety of important 2D topological physics in a 1D array of optical cavities. This application for orbital angular momentum of light not only reduces required physical resources but also increases feasible scale of simulation, and thus makes it possible to investigate important topics such as edge-state transport and topological phase transition in a small simulator ready for immediate experimental exploration.

Stable Solitons in Three Dimensional Free Space without the Ground State: Self-Trapped Bose-Einstein Condensates with Spin-Orbit Coupling.

By means of variational methods and systematic numerical analysis, we demonstrate the existence of metastable solitons in three dimensional (3D) free space, in the context of binary atomic condensates combining contact self-attraction and spin-orbit coupling, which can be engineered by available experimental techniques. Depending on the relative strength of the intra- and intercomponent attraction, the stable solitons feature a semivortex or mixed-mode structure. In spite of the fact that the local cubic self-attraction gives rise to the supercritical collapse in 3D, and hence the setting produces no true ground state, the solitons are stable against small perturbations, motion, and collisions.

Causal interactions between fronto-parietal central executive and default-mode networks in humans.

Information processing during human cognitive and emotional operations is thought to involve the dynamic interplay of several large-scale neural networks, including the fronto-parietal central executive network (CEN), cingulo-opercular salience network (SN), and the medial prefrontal-medial parietal default mode networks (DMN). It has been theorized that there is a causal neural mechanism by which the CEN/SN negatively regulate the DMN. Support for this idea has come from correlational neuroimaging studies; however, direct evidence for this neural mechanism is lacking. Here we undertook a direct test of this mechanism by combining transcranial magnetic stimulation (TMS) with functional MRI to causally excite or inhibit TMS-accessible prefrontal nodes within the CEN or SN and determine consequent effects on the DMN. Single-pulse excitatory stimulations delivered to only the CEN node induced negative DMN connectivity with the CEN and SN, consistent with the CEN/SN's hypothesized negative regulation of the DMN. Conversely, low-frequency inhibitory repetitive TMS to the CEN node resulted in a shift of DMN signal from its normally low-frequency range to a higher frequency, suggesting disinhibition of DMN activity. Moreover, the CEN node exhibited this causal regulatory relationship primarily with the medial prefrontal portion of the DMN. These findings significantly advance our understanding of the causal mechanisms by which major brain networks normally coordinate information processing. Given that poorly regulated information processing is a hallmark of most neuropsychiatric disorders, these findings provide a foundation for ways to study network dysregulation and develop brain stimulation treatments for these disorders.

Quantum computation with untunable couplings.

Most quantum computer realizations require the ability to apply local fields and tune the couplings between qubits, in order to realize single bit and two bit gates which are necessary for universal quantum computation. We present a scheme to remove the necessity of switching the couplings between qubits for two bit gates, which are more costly in many cases. Our strategy is to compute with encoded qubits in and out of carefully designed interaction free subspaces analogous to decoherence free subspaces. We give two examples to show how universal quantum computation is realized in our scheme with local manipulations to physical qubits only, for both diagonal and off diagonal interactions.