Magnetically controllable multimode interference in topological photonic crystals.

Topological photonic insulators show promise for applications in compact integrated photonic circuits due to their ability to transport light robustly through sharp bendings. The number of topological edge states relies on the difference between the bulk Chern numbers across the boundary, as dictated by the bulk edge correspondence. The interference among multiple topological edge modes in topological photonics systems may allow for controllable functionalities that are particularly desirable for constructing reconfigurable photonic devices. In this work, we demonstrate magnetically controllable multimode interference based on gyromagnetic topological photonic insulators that support two unidirectional edge modes with different dispersions. We successfully achieve controllable power splitting in experiments by engineering multimode interference with the magnetic field intensity or the frequency of wave. Our work demonstrates that manipulating the interference among multiple chiral edge modes can facilitate the advancement of highly efficient and adaptable microwave devices.

Enhancing the Versatility and Performance of Soft Robotic Grippers, Hands, and Crawling Robots Through Three-Dimensional-Printed Multifunctional Buckling Joints.

Soft robotic grippers and hands offer adaptability, lightweight construction, and enhanced safety in human-robot interactions. In this study, we introduce vacuum-actuated soft robotic finger joints to overcome their limitations in stiffness, response, and load-carrying capability. Our design-optimized through parametric design and three-dimensional (3D) printing-achieves high stiffness using vacuum pressure and a buckling mechanism for large bending angles (>90°) and rapid response times (0.24 s). We develop a theoretical model and nonlinear finite-element simulations to validate the experimental results and provide valuable insights into the underlying mechanics and visualization of the deformation and stress field. We showcase versatile applications of the buckling joints: a three-finger gripper with a large lifting ratio (∼96), a five-finger robotic hand capable of replicating human gestures and adeptly grasping objects of various characteristics in static and dynamic scenarios, and a planar-crawling robot carrying loads 30 times its weight at 0.89 body length per second (BL/s). In addition, a jellyfish-inspired robot crawls in circular pipes at 0.47 BL/s. By enhancing soft robotic grippers' functionality and performance, our study expands their applications and paves the way for innovation through 3D-printed multifunctional buckling joints.

Experimental realization of chiral Landau levels in two-dimensional Dirac cone systems with inhomogeneous effective mass.

Chiral zeroth Landau levels are topologically protected bulk states. In particle physics and condensed matter physics, the chiral zeroth Landau level plays a significant role in breaking chiral symmetry and gives rise to the chiral anomaly. Previous experimental works on such chiral Landau levels are mainly based on three-dimensional Weyl degeneracies coupled with axial magnetic fields. Their realizations using two-dimensional Dirac point systems, being more promising for future applications, were never experimentally realized before. Here we propose an experimental scheme for realizing chiral Landau levels in a two-dimensional photonic system. By introducing an inhomogeneous effective mass through breaking local parity-inversion symmetries, a synthetic in-plane magnetic field is generated and coupled with the Dirac quasi-particles. Consequently, the zeroth-order chiral Landau levels can be induced, and the one-way propagation characteristics are experimentally observed. In addition, the robust transport of the chiral zeroth mode against defects in the system is also experimentally tested. Our system provides a new pathway for the realization of chiral Landau levels in two-dimensional Dirac cone systems, and may potentially be applied in device designs utilizing the chiral response and transport robustness.

Geometrical Theory of Electromagnetic Nonreciprocity.

Recent advances in electromagnetic nonreciprocity raise the question of how to engineer the nonreciprocal electromagnetic response with geometrical approaches. In this Letter, we examine this problem by introducing generalized electromagnetic continua consisting structured points, which carry extra degrees of freedom over coordinate transformation. We show that general nonreciprocal media have a unique time-varying Riemannian metric structure with local spinning components. It is demonstrated that the nonreciprocity can be alternatively identified as the torsion tensor of a Riemann-Cartan space, which could provide analytic expressions for the magneto-optical effect and the axionic magnetoelectric coupling. Our theory not only gives a deeper insight into the fundamental understanding of electromagnetic nonreciprocity but also provides a practical principle to geometrically design nonreciprocal devices through frame transformation.

On-chip integrated exceptional surface microlaser.

The on-chip integrated visible microlaser is a core unit of high-speed visible-light communication with huge bandwidth resources, which needs robustness against fabrication errors, compressible linewidth, reducible threshold, and in-plane emission. However, until now, it has been a great challenge to meet these requirements simultaneously. Here, we report a scalable strategy to realize a robust on-chip integrated visible microlaser with further improved lasing performances enabled by the increased orders (n) of exceptional surfaces, and experimentally verify the strategy by demonstrating the performances of a second-order exceptional surface-tailored microlaser. We further prove the potential application of the strategy by discussing an exceptional surface-tailored topological microlaser with unique performances. This work lays a foundation for further development of on-chip integrated high-speed visible-light communication and processing systems, provides a platform for the fundamental study of non-Hermitian photonics, and proposes a feasible method of joint research for non-Hermitian photonics with nonlinear optics and topological photonics.

Stable optical lateral forces from inhomogeneities of the spin angular momentum.

Transverse spin momentum related to the spin angular momentum (SAM) of light has been theoretically studied recently and predicted to generate an intriguing optical lateral force (OLF). Despite extensive studies, there is no direct experimental evidence of a stable OLF resulting from the dominant SAM rather than the ubiquitous spin-orbit interaction in a single light beam. Here, we theoretically unveil the nontrivial physics of SAM-correlated OLF, showing that the SAM is a dominant factor for the OLF on a nonabsorbing particle, while an additional force from the canonical (orbital) momentum is exhibited on an absorbing particle due to the spin-orbit interaction. Experimental results demonstrate the bidirectional movement of 5-µm-diameter particles on both sides of the beam with opposite spin momenta. The amplitude and sign of this force strongly depend on the polarization. Our optofluidic platform advances the exploitation of exotic forces in systems with a dominant SAM, facilitating the exploration of fascinating light-matter interactions.

Inverse Optical Torques on Dielectric Nanoparticles in Elliptically Polarized Light Waves.

Elliptically polarized light waves carry the spin angular momentum (SAM), so they can exert optical torques on nanoparticles. Usually, the rotation follows the same direction as the SAM due to momentum conservation. It is counterintuitive to observe the reversal of optical torque acting on an ordinary dielectric nanoparticle illuminated by an elliptically or circularly polarized light wave. Here, we demonstrate that negative optical torques, which are opposite to the direction of SAM, can ubiquitously emerge when elliptically polarized light waves are impinged on dielectric nanoparticles obliquely. Intriguingly, the rotation can be switched between clockwise and counterclockwise directions by controlling the incident angle of light. Our study suggests a new playground to harness polarization-dependent optical force and torque for advancing optical manipulations.

Merging bound states in the continuum by harnessing higher-order topological charges.

Bound states in the continuum (BICs) can confine light with a theoretically infinite Q factor. However, in practical on-chip resonators, scattering loss caused by inevitable fabrication imperfection leads to finite Q factors due to the coupling of BICs with nearby radiative states. Merging multiple BICs can improve the robustness of BICs against fabrication imperfection by improving the Q factors of nearby states over a broad wavevector range. To date, the studies of merging BICs have been limited to fundamental BICs with topological charges ±1. Here we show the unique advantages of higher-order BICs (those with higher-order topological charges) in constructing merging BICs. Merging multiple BICs with a higher-order BIC can further improve the Q factors compared with those involving only fundamental BICs. In addition, higher-order BICs offer great flexibility in realizing steerable off-Γ merging BICs. A higher-order BIC at Γ can split into a few off-Γ fundamental BICs by reducing the system symmetry. The split BICs can then be tuned to merge with another BIC, e.g., an accidental BIC, at an off-Γ point. When the in-plane mirror symmetry is further broken, merging BICs become steerable in the reciprocal space. Merging BICs provide a paradigm to achieve robust ultrahigh-Q resonances, which are important in enhancing nonlinear and quantum effects and improving the performance of optoelectronic devices.

(Pro)renin Receptor Knockdown Attenuates Liver Fibrosis Through Inactivation of ERK/TGF-ß1/SMAD3 Pathway.

BACKGROUND & AIMS: Activation of the (pro)renin receptor (PRR) up-regulates the expression of profibrotic genes in the kidney and heart. We aimed to investigate the role of PRR in hepatic fibrogenesis. METHODS: Human hepatic PRR levels were measured in patients with or without liver fibrosis. PRR expression was analyzed in primary mouse hepatic stellate cells (HSCs). Experimental fibrosis was studied in thioacetamide (TAA)-treated or methionine choline-deficient (MCD) diet-fed C57BL/6 mice. Lentivirus-mediated PRR short hairpin RNA was used to knockdown hepatic PRR expression. Lentiviral vectors expressing PRR short hairpin RNA or complementary DNA from the α-smooth muscle actin promoter were used for myofibroblast-specific gene knockdown or overexpression. RESULTS: PRR is up-regulated in human and mouse fibrotic livers, and in activated HSCs. Hepatic PRR knockdown reduced liver fibrosis by suppressing the activation of HSCs and expression of profibrotic genes in TAA or MCD diet-injured mice without significant changes in hepatic inflammation. Renin and prorenin increased the expression of PRR and production of TGF-ß1 in human activated HSC Lieming Xu-2 cells, and knockdown of PRR inactivated Lieming Xu-2 cells with decreased production of transforming growth factor (TGF)-ß1 and Mothers against decapentaplegic homolog 3 (Smad3) phosphorylation. Myofibroblast-specific PRR knockdown also attenuated liver fibrosis in TAA or MCD diet-injured mice. Mice with both myofibroblast-specific and whole-liver PRR knockdown showed down-regulation of the hepatic extracellular signal-regulated kinase (ERK)/TGF-ß1/Smad3 pathway. Myofibroblast-specific PRR overexpression worsened TAA-induced liver fibrosis by up-regulating the ERK/TGF-ß1/Smad3 pathway. CONCLUSIONS: PRR contributes to liver fibrosis and HSC activation, and its down-regulation attenuates liver fibrosis through inactivation of the ERK/TGF-ß1/Smad3 pathway. Therefore, PRR is a promising therapeutic target for liver fibrosis.

Exceptional cones in 4D parameter space.

The notion of synthetic dimensions has expanded the realm of topological physics to four dimensional (4D) space lately. In this work, non-Hermiticity is used as a synthetic parameter in PT-symmetric photonic crystals to study the topological physics in 4D non-Hermitian synthetic parameter space. We realize a 3D exceptional hypersurface (EHS) in such 4D parameter space, and the degeneracy points emerge due to the symmetry of synthetic parameters. We further demonstrate the existence of exceptional degenerate points (EDPs) on the EHS that originates from the chirality of exceptional points (EPs), and the exceptional surface near EDPs behaves like a Dirac cone. We further show that a very narrow reflection plateau can be found near these EDPs, and their sensitivity towards the PT-symmetry breaking environmental perturbation can make these degeneracy points useful in optical sensing and many other nonlinear and quantum optical applications.

Broadband Microwave Absorption by Logarithmic Spiral Metasurface.

Metamaterials have enabled the design of electromagnetic wave absorbers with unprecedented performance. Conventional metamaterial absorbers usually employ multiple structure components in one unit cell to achieve broadband absorption. Here, a simple metasurface microwave absorber is proposed that has one metal-backed logarithmic spiral resonator as the unit cell. It can absorb >95% of normally incident microwave energy within the frequency range of 6 GHz-37 GHz as a result of the scale invariant geometry and the Fabry-Perot-type resonances of the resonator. The thickness of the metasurface is 5 mm and approaches the Rozanov limit of an optimal absorber. The physics underlying the broadband absorption is discussed. A comparison with Archimedean spiral metasurface is conducted to uncover the crucial role of scale invariance. The study opens a new direction of electromagnetic wave absorption by employing the scale invariance of Maxwell equations and may also be applied to the absorption of other classical waves such as sound.

Nanophotonic Array-Induced Dynamic Behavior for Label-Free Shape-Selective Bacteria Sieving.

Current particle sorting methods such as microfluidics, acoustics, and optics focus on exploiting the differences in the mass, size, refractive index, or fluorescence staining. However, there exist formidable challenges for them to sort label-free submicron particles with similar volume and refractive index yet distinct shapes. In this work, we report an optofluidic nanophotonic sawtooth array (ONSA) that generates sawtooth-like light fields through light coupling, paving the physical foundation for shape-selective sieving. Submicron particles interact with the coupled hotspots which impose different optical torques on the particles according to their shapes. Unstained S. aureus and E. coli are used as a model system to demonstrate this shape-selective sorting mechanism based on the torque-induced body dynamics, which was previously unattainable by other particle sorting technologies. More than 95% of S. aureus is retained within ONSA, while more than 97% of E. coli is removed. This nanophotonic chip offers a paradigm shift in shape-selective sorting of submicron particles and expands the boundary of optofluidics-based particle manipulation.

Human relaxin-2 attenuates hepatic steatosis and fibrosis in mice with non-alcoholic fatty liver disease.

Human relaxin-2 reduces hepatic fibrosis in mice. However, the effects of relaxin-2 on hepatic steatosis and fibrosis in animals with non-alcoholic fatty liver disease (NAFLD) remain to be elucidated. C57BL/6 mice fed a high-fat diet (HFD) or methionine-choline-deficient (MCD) diet were randomly assigned to receive recombinant human relaxin-2 (25 or 75 µg/kg/day) or vehicle for 4 weeks. In HFD-fed mice, relaxin-2 decreased systemic insulin resistance and reduced body weight, epididymal fat mass and serum leptin and insulin concentrations. In livers of HFD-fed mice, relaxin-2 attenuated steatosis and increased phosphorylation of insulin receptor substrate-1, Akt and endothelial nitric oxide synthase (eNOS), and activated genes that regulate fatty acid oxidation and suppressed acetyl-CoA carboxylase. Relaxin-2 had no direct anti-steatotic effect on primary mouse hepatocytes, but S-nitroso-N-acetylpenicillamine attenuated palmitic acid-induced steatosis and activated genes regulating fatty acid oxidation in hepatocytes. In mice fed an MCD diet, relaxin-2 attenuated steatosis, inflammation and fibrosis. Relaxin-2 increased eNOS and Akt phosphorylation and transcript levels of cytochrome P450-4a10 and decreased acetyl-CoA carboxylase in MCD-fed mouse livers. Moreover, expression levels of Kupffer cell activation, hepatic stellate cell activation and hepatocyte apoptosis were decreased in MCD diet-fed mice receiving relaxin-2. In conclusion, relaxin-2 reduces hepatic steatosis by activating intrahepatic eNOS in HFD-fed mice and further attenuates liver fibrosis in MCD diet-fed mice. Therefore, human relaxin-2 is a potential therapeutic treatment for NAFLD.

Dabigatran Reduces Liver Fibrosis in Thioacetamide-Injured Rats.

BACKGROUND: Liver fibrosis can progress to cirrhosis, hepatocellular carcinoma, or liver failure. Unfortunately, the antifibrotic agents are limited. Thrombin activates hepatic stellate cells (HSCs). Therefore, we investigated the effects of a direct thrombin inhibitor, dabigatran, on liver fibrosis. METHODS: Adult male Sprague-Dawley rats were injected intraperitoneally with thioacetamide (TAA, 200 mg/kg twice per week) for 8 or 12 weeks to induce liver fibrosis. The injured rats were assigned an oral gavage of dabigatran etexilate (30 mg/kg/day) or vehicle in the last 4 weeks of TAA administration. Rats receiving an injection of normal saline and subsequent oral gavage of dabigatran etexilate or vehicle served as controls. RESULTS: In the 8-week TAA-injured rats, dabigatran ameliorated fibrosis, fibrin deposition, and phosphorylated ERK1/2 in liver, without altering the transcript expression of thrombin receptor protease-activated receptor-1. In vitro, dabigatran inhibited thrombin-induced HSC activation. Furthermore, dabigatran reduced intrahepatic angiogenesis and portal hypertension in TAA-injured rats. Similarly, in the 12-week TAA-injured rats, a 4-week treatment with dabigatran reduced liver fibrosis and portal hypertension. CONCLUSIONS: By inhibiting thrombin action, dabigatran reduced liver fibrosis and intrahepatic angiogenesis. Dabigatran may be a promising therapeutic agent for treatment of liver fibrosis.

Middle East respiratory syndrome coronavirus and bat coronavirus HKU9 both can utilize GRP78 for attachment onto host cells.

Coronavirus tropism is predominantly determined by the interaction between coronavirus spikes and the host receptors. In this regard, coronaviruses have evolved a complicated receptor-recognition system through their spike proteins. Spikes from highly related coronaviruses can recognize distinct receptors, whereas spikes of distant coronaviruses can employ the same cell-surface molecule for entry. Moreover, coronavirus spikes can recognize a broad range of cell-surface molecules in addition to the receptors and thereby can augment coronavirus attachment or entry. The receptor of Middle East respiratory syndrome coronavirus (MERS-CoV) is dipeptidyl peptidase 4 (DPP4). In this study, we identified membrane-associated 78-kDa glucose-regulated protein (GRP78) as an additional binding target of the MERS-CoV spike. Further analyses indicated that GRP78 could not independently render nonpermissive cells susceptible to MERS-CoV infection but could facilitate MERS-CoV entry into permissive cells by augmenting virus attachment. More importantly, by exploring potential interactions between GRP78 and spikes of other coronaviruses, we discovered that the highly conserved human GRP78 could interact with the spike protein of bat coronavirus HKU9 (bCoV-HKU9) and facilitate its attachment to the host cell surface. Taken together, our study has identified GRP78 as a host factor that can interact with the spike proteins of two Betacoronaviruses, the lineage C MERS-CoV and the lineage D bCoV-HKU9. The capacity of GRP78 to facilitate surface attachment of both a human coronavirus and a phylogenetically related bat coronavirus exemplifies the need for continuous surveillance of the evolution of animal coronaviruses to monitor their potential for human adaptations.

Topological transport of sound mediated by spin-redirection geometric phase.

When a dynamic system undergoes a cyclic evolution, a geometric phase that depends only on the path traversed in parameter space can arise in addition to the normal dynamical phase. These geometric phases have profound impacts in both quantum and classical physics. In addition to the geometric phase associated with band structures in reciprocal space that has led to the discovery of topological insulators, the spin-redirection geometric phase induced by the SO(3) rotation of states in real space can also give rise to intriguing phenomena such as the photonic analog of the spin Hall effect. By exploiting the orbital angular momentum of sound vortices, we theoretically and experimentally demonstrate the spin-redirection geometric phase effects in airborne sound, which is a scalar wave without spin. We show that these effects, associated with the helical transport of sound, can be used to control the flow of sound. This finding opens new possibilities for the manipulation of scalar wave propagation by exploiting spin-redirection geometric phases.

Nanofibrous scaffolds for the guidance of stem cell-derived neurons for auditory nerve regeneration.

Impairment of spiral ganglion neurons (SGNs) of the auditory nerve is a major cause for hearing loss occurring independently or in addition to sensory hair cell damage. Unfortunately, mammalian SGNs lack the potential for autonomous regeneration. Stem cell based therapy is a promising approach for auditory nerve regeneration, but proper integration of exogenous cells into the auditory circuit remains a fundamental challenge. Here, we present novel nanofibrous scaffolds designed to guide the integration of human stem cell-derived neurons in the internal auditory meatus (IAM), the foramen allowing passage of the spiral ganglion to the auditory brainstem. Human embryonic stem cells (hESC) were differentiated into neural precursor cells (NPCs) and seeded onto aligned nanofiber mats. The NPCs terminally differentiated into glutamatergic neurons with high efficiency, and neurite projections aligned with nanofibers in vitro. Scaffolds were assembled by seeding GFP-labeled NPCs on nanofibers integrated in a polymer sheath. Biocompatibility and functionality of the NPC-seeded scaffolds were evaluated in vivo in deafened guinea pigs (Cavia porcellus). To this end, we established an ouabain-based deafening procedure that depleted an average 72% of SGNs from apex to base of the cochleae and caused profound hearing loss. Further, we developed a surgical procedure to implant seeded scaffolds directly into the guinea pig IAM. No evidence of an inflammatory response was observed, but post-surgery tissue repair appeared to be facilitated by infiltrating Schwann cells. While NPC survival was found to be poor, both subjects implanted with NPC-seeded and cell-free control scaffolds showed partial recovery of electrically-evoked auditory brainstem thresholds. Thus, while future studies must address cell survival, nanofibrous scaffolds pose a promising strategy for auditory nerve regeneration.

Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 Is an Important Surface Attachment Factor That Facilitates Entry of Middle East Respiratory Syndrome Coronavirus.

UNLABELLED: The spike proteins of coronaviruses are capable of binding to a wide range of cellular targets, which contributes to the broad species tropism of coronaviruses. Previous reports have demonstrated that Middle East respiratory syndrome coronavirus (MERS-CoV) predominantly utilizes dipeptidyl peptidase 4 (DPP4) for cell entry. However, additional cellular binding targets of the MERS-CoV spike protein that may augment MERS-CoV infection have not been further explored. In the current study, using the virus overlay protein binding assay (VOPBA), we identified carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as a novel cell surface binding target of MERS-CoV. CEACAM5 coimmunoprecipitated with the spike protein of MERS-CoV in both overexpressed and endogenous settings. Disrupting the interaction between CEACAM5 and MERS-CoV spike with anti-CEACAM5 antibody, recombinant CEACAM5 protein, or small interfering RNA (siRNA) knockdown of CEACAM5 significantly inhibited the entry of MERS-CoV. Recombinant expression of CEACAM5 did not render nonpermissive baby hamster kidney (BHK21) cells susceptible to MERS-CoV infection. Instead, CEACAM5 overexpression significantly enhanced the attachment of MERS-CoV to the BHK21 cells. More importantly, the entry of MERS-CoV was increased when CEACAM5 was overexpressed in permissive cells, which suggested that CEACAM5 could facilitate MERS-CoV entry in conjunction with DPP4 despite not being able to support MERS-CoV entry independently. Taken together, the results of our study identified CEACAM5 as a novel cell surface binding target of MERS-CoV that facilitates MERS-CoV infection by augmenting the attachment of the virus to the host cell surface. IMPORTANCE: Infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with the highest mortality rate among all known human-pathogenic coronaviruses. Currently, there are no approved vaccines or therapeutics against MERS-CoV infection. The identification of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as a novel cell surface binding target of MERS-CoV advanced our knowledge on the cell binding biology of MERS-CoV. Importantly, CEACAM5 could potentiate the entry of MERS-CoV by functioning as an attachment factor. In this regard, CEACAM5 could serve as a novel target, in addition to dipeptidyl peptidase-4 (DPP4), in the development of antiviral strategies for MERS-CoV.

Electromagnetic stress at the boundary: Photon pressure or tension?

It is well known that incident photons carrying momentum ℏk exert a positive photon pressure. But if light is impinging from a negative refractive medium in which ℏk is directed toward the source of radiation, should light exert a photon "tension" instead of a photon pressure? Using an ab initio method that takes the underlying microstructure of a material into account, we find that when an electromagnetic wave propagates from one material into another, the electromagnetic stress at the boundary is, in fact, indeterminate if only the macroscopic parameters are specified. Light can either pull or push the boundary, depending not only on the macroscopic parameters but also on the microscopic lattice structure of the polarizable units that constitute the medium. Within the context of an effective-medium approach, the lattice effect is attributed to electrostriction and magnetostriction, which can be accounted for by the Helmholtz stress tensor if we use the macroscopic fields to calculate the boundary optical stress.

Hemagglutinin of influenza A virus binds specifically to cell surface nucleolin and plays a role in virus internalization.

The hemagglutinin (HA) protein of influenza A virus initiates cell entry by binding to sialic acids on target cells. In the current study, we demonstrated that in addition to sialic acids, influenza A/Puerto Rico/8/34 H1N1 (PR8) virus HA specifically binds to cell surface nucleolin (NCL). The interaction between HA and NCL was initially revealed with virus overlay protein binding assay (VOPBA) and subsequently verified with co-immunoprecipitation. Importantly, inhibiting cell surface NCL with NCL antibody, blocking PR8 viruses with purified NCL protein, or depleting endogenous NCL with siRNA all substantially reduced influenza virus internalization. We further demonstrated that NCL was a conserved cellular factor required for the entry of multiple influenza A viruses, including H1N1, H3N2, H5N1, and H7N9. Overall, our findings identified a novel role of NCL in influenza virus life cycle and established NCL as one of the host cell surface proteins for the entry of influenza A virus.