Observation of intrinsic chiral bound states in the continuum.

Photons with spin angular momentum possess intrinsic chirality, which underpins many phenomena including nonlinear optics1, quantum optics2, topological photonics3 and chiroptics4. Intrinsic chirality is weak in natural materials, and recent theoretical proposals5-7 aimed to enlarge circular dichroism by resonant metasurfaces supporting bound states in the continuum that enhance substantially chiral light-matter interactions. Those insightful works resort to three-dimensional sophisticated geometries, which are too challenging to be realized for optical frequencies8. Therefore, most of the experimental attempts9-11 showing strong circular dichroism rely on false/extrinsic chirality by using either oblique incidence9,10 or structural anisotropy11. Here we report on the experimental realization of true/intrinsic chiral response with resonant metasurfaces in which the engineered slant geometry breaks both in-plane and out-of-plane symmetries. Our result marks, to our knowledge, the first observation of intrinsic chiral bound states in the continuum with near-unity circular dichroism of 0.93 and a high quality factor exceeding 2,663 for visible frequencies. Our chiral metasurfaces may lead to a plethora of applications in chiral light sources and detectors, chiral sensing, valleytronics and asymmetric photocatalysis.

The Investigation of Neuromimetic Dynamics in Ferroelectrics via In Situ TEM.

The core task of neuromorphic devices is to effectively simulate the behavior of neurons and synapses. Based on the functionality of ferroelectric domains with the advantages of low power consumption and high-speed response, great progress has been made in realizing neuromimetic behaviors such as ferroelectric synaptic devices. However, the correlation between the ferroelectric domain dynamics and neuromimetic behavior remains unclear. Here, we reveal the correlation between domain/domain wall dynamics and neuromimetic behaviors from a microscopic perspective in real-time by using high temporal and spatial resolution in situ transmission electron microscopy. Furthermore, we propose utilizing ferroelectric microstructures for the simultaneous simulation of neuronal and synaptic plasticity, which is expected to improve the integration and performance of ferroelectric neuromorphic devices. We believe that this work to study neuromimetic behavior from the perspective of domain dynamics is instructive for the development of ferroelectric neuromorphic devices.

Compact spin-valley-locked perovskite emission.

Circularly polarized light sources with free-space directional emission play a key role in chiroptics1, spintronics2, valleytronics3 and asymmetric photocatalysis4. However, conventional approaches fail to simultaneously realize pure circular polarization, high directionality and large emission angles in a compact emitter. Metal-halide perovskite semiconductors are promising light emitters5-8, but the absence of an intrinsic spin-locking mechanism results in poor emission chirality. Further, device integration has undermined the efficiency and directionality of perovskite chiral emitters. Here we realize compact spin-valley-locked perovskite emitting metasurfaces where spin-dependent geometric phases are imparted into bound states in the continuum via Brillouin zone folding, and thus, photons with different spins are selectively addressed to opposite valleys. Employing this approach, chiral purity of 0.91 and emission angle of 41.0° are simultaneously achieved, with a beam divergence angle of 1.6°. With this approach, we envisage the realization of chiral light-emitting diodes, as well as the on-chip generation of entangled photon pairs.

The motion of micro-swimmers over a cavity in a micro-channel.

This article combines the lattice Boltzmann method (LBM) with the squirmer model to investigate the motion of micro-swimmers in a channel-cavity system. The study analyses various influential factors, including the value of the squirmer-type factor (ß), the swimming Reynolds number (Rep), the size of the cavity, initial position and particle size on the movement of micro-swimmers within the channel-cavity system. We simultaneously studied three types of squirmer models, Puller (ß > 0), Pusher (ß < 0), and Neutral (ß = 0) swimmers. The findings reveal that the motion of micro-swimmers is determined by the value of ß and Rep, which can be classified into six distinct motion modes. For Puller and Pusher, when the ß value is constant, an increase in Rep will lead to transition in the motion mode. Moreover, the appropriate depth of cavity within the channel-cavity system plays a crucial role in capturing and separating Neutral swimmers. This study, for the first time, explores the effect of complex channel-cavity systems on the behaviour of micro-swimmers and highlights their separation and capture ability. These findings offer novel insights for the design and enhancement of micro-channel structures in achieving efficient separation and capture of micro-swimmers.

Evolution and global charge conservation for polarization singularities emerging from non-Hermitian degeneracies.

Core concepts in singular optics, especially the polarization singularities, have rapidly penetrated the surging fields of topological and non-Hermitian photonics. For open photonic structures with non-Hermitian degeneracies in particular, polarization singularities would inevitably encounter another sweeping concept of Berry phase. Several investigations have discussed, in an inexplicit way, connections between both concepts, hinting at that nonzero topological charges for far-field polarizations on a loop are inextricably linked to its nontrivial Berry phase when degeneracies are enclosed. In this work, we reexamine the seminal photonic crystal slab that supports the fundamental two-level non-Hermitian degeneracies. Regardless of the invariance of nontrivial Berry phase (concerning near-field Bloch modes defined on the momentum torus) for different loops enclosing both degeneracies, we demonstrate that the associated far polarization fields (defined on the momentum sphere) exhibit topologically inequivalent patterns that are characterized by variant topological charges, including even the trivial scenario of zero charge. Moreover, the charge carried by the Fermi arc actually is not well defined, which could be different on opposite bands. It is further revealed that for both bands, the seemingly complex evolutions of polarizations are bounded by the global charge conservation, with extra points of circular polarizations playing indispensable roles. This indicates that although not directly associated with any local charges, the invariant Berry phase is directly linked to the globally conserved charge, physical principles underlying which have all been further clarified by a two-level Hamiltonian with an extra chirality term. Our work can potentially trigger extra explorations beyond photonics connecting Berry phase and singularities.

Emergent Mechanics of Magnetic Skyrmions Deformed by Defects.

While magnetic skyrmions are often modeled as rigid particles, both experiments and micromagnetic simulations indicate their easy-to-deform characteristic, especially when their motion is restricted by defects. Here we establish a theoretical framework for the dynamics of magnetic skyrmions by incorporating the degrees of freedom related to deformation and predict well the current-driven dynamics of deformable skyrmions in the presence of line defects without any parameter fitting, where classical theories based on rigid-particle assumption deviate significantly. Further, we define an emergent property of magnetic skyrmions-flexibility and show that this property strongly modulates the depinning dynamics of skyrmions along a line defect with breaches. Our work explores the emergent mechanics of magnetic skyrmions and extends the current understanding on the dynamics of skyrmions interacted with defects.

Non-Hermitian Chiral Heat Transport.

Exceptional point (EP) has been captivated as a concept of interpreting eigenvalue degeneracy and eigenstate exchange in non-Hermitian physics. The chirality in the vicinity of EP is intrinsically preserved and usually immune to external bias or perturbation, resulting in the robustness of asymmetric backscattering and directional emission in classical wave fields. Despite recent progress in non-Hermitian thermal diffusion, all state-of-the-art approaches fail to exhibit chiral states or directional robustness in heat transport. Here we report the first discovery of chiral heat transport, which is manifested only in the vicinity of EP but suppressed at the EP of a thermal system. The chiral heat transport demonstrates significant robustness against drastically varying advections and thermal perturbations imposed. Our results reveal the chirality in heat transport process and provide a novel strategy for manipulating mass, charge, and diffusive light.

A novel synthetic method for backbone-cyclized polypeptide POL7080 with the help of hydrophobic-support materials.

Murepavadin (POL7080) in phase III clinical trials, a backbone-cyclized polypeptide composed of 14 amino acids, has a novel mode of action and shows a specific and efficient bactericidal effect against multidrug-resistant Pseudomonas aeruginosa. It is a potential candidate to treat severe P. aeruginosa infections in the future and still has significant commercial value for further research and development. In this paper, we report a liquid-phase peptide synthetic route for this valuable candidate polypeptide assisted by hydrophobic-support materials (tags), which overcomes the difficulties of high cost and poor yield in the traditional solid-phase synthesis of macrocyclic peptides. Through the careful optimization of reaction conditions and the innovative strategy of synthetic post-treatment, we established a simple and efficient liquid-phase synthetic route suitable for POL7080 and other similar structures, with satisfactory yield, high purity and a production process not being controlled by scale.

Design, synthesis and evaluation of oxazolopyridinone derivatives as quorum sensing inhibitors.

The antibiotic crisis is associated with the appearance of multidrug resistant (MDR) pathogens, which has caused severe bacterial infections and imposed a huge burden on modern society. Therefore, there is an urgent need to develop new antibacterial drugs with novel mechanism of action. Here we designed and synthesized three series of benzoxazolone, oxazolopyridinone and 3-(2-hydroxyphenyl)hydantoin derivatives and evaluated their activity as novel quorum sensing (QS) inhibitors. We found that benzoxazolone and oxazolopyridinone derivatives had promising QS inhibitory activity in the minimum inhibitory concentration, pyocyanin and rhamnolipid inhibition assays. In particular, A10 and B20 at 256 µg/mL not only suppressed pyocyanin production regulated by QS in P. aeruginosa PAO1 by 36.55% and 46.90%, respectively, but also showed the strongest rhamnolipid inhibitory activity with the IC50 values of 66.35 and 56.75 µg/mL, respectively. Further studies demonstrated that B20 at 64 µg/mL inhibited biofilm formation in P. aeruginosa PAO1 by 40%, and weakened its swarming motility. More importantly, the bacterial mortality of B20 combined with ciprofloxacin and clarithromycin against P. aeruginosa were 48.27% and 49.79%, respectively, while ciprofloxacin and clarithromycin had only 16.99% and 29.11% of bacterial mortality against P. aeruginosa when used alone. Mechanistic studies indicated that B20 directly inhibited the QS pathway based on the GFP reporter strain assay. Overall, this compound with oxazolopyridinone core could serve as an antibacterial lead of QS inhibitor for further evaluation of its drug-likeness.

Direct Observation of Spin-Orbit Interaction of Light via Chiroptical Responses.

The spin-orbit interaction of light is a fundamental manifestation of controlling its angular momenta with numerous applications in photonic spin Hall effects and chiral quantum optics. However, observation of an optical spin Hall effect, which is normally very weak with subwavelength displacements, needs quantum weak measurements or sophisticated metasurfaces. Here, we theoretically and experimentally demonstrate the spin-orbit interaction of light in the form of strong chiroptical responses by breaking the in-plane inversion symmetry of a dielectric substrate. The chiroptical signal is observed at the boundary of a microdisk illuminated by circularly polarized vortex beams at normal incidence. The generated chiroptical spectra are tunable for different photonic orbital angular momenta and microdisk diameters. Our findings, correlating photonic spin-orbit interaction with chiroptical responses, may provide a route for exploiting optical information processing, enantioselective sensing, and chiral metrology.

Flexoresponses of Synthetic Antiferromagnetic Systems Hosting Skyrmions.

While strain gradients break lattice centrosymmetry, ferromagnetism is a time-reversal symmetry breaking product. Flexomagnetic effect in ferromagnets is usually indirect and weak. In this Letter, we reveal a topologically enhanced flexomagnetic effect in synthetic antiferromagnetic systems based on Dzyaloshinskii-Moriya interaction and the large deformability of skyrmion. Moreover, the synthetic antiferromagnetic skyrmion exhibits an unexpected Hall effect under strain gradient. We propose that this flexo-Hall effect originates from a geometric Magnus force related to the asymmetric deformation of skyrmion. Our results shed new insights into the flexoresponses in systems hosting topological structures and may open up a new field-"flexoskyrmionics".

Can Weak Chirality Induce Strong Coupling between Resonant States?

Strong coupling between resonant states is usually achieved by modulating intrinsic parameters of optical systems, e.g., the refractive index of constituent materials or structural geometries. Externally introduced chiral enantiomers may couple resonances, but the extremely weak chirality of natural enantiomers largely prevents the system from reaching strong coupling regimes. Whether weak chirality could induce strong coupling between resonant states remains an open question. Here, we realize strong coupling between quasibound states in the continuum of a high-Q metasurface, assisted with externally introduced enantiomers of weak chirality. We establish a chirality-involved Hamiltonian to quantitatively describe the correlation between the coupling strength and the chirality of such systems, which provides an insightful recipe for enhancing the coupling of resonant states further in the presence of quite weak chirality. Consequently, high-sensitivity chiral sensing is demonstrated, in which the circular dichroism signal is enhanced 3 orders higher than the case without strong coupling. Our findings present a distinct strategy for manipulating optical coupling between resonances, revealing opportunities in chiral sensing, topological photonics, and quantum optics.

Riemann-Encircling Exceptional Points for Efficient Asymmetric Polarization-Locked Devices.

Dynamically encircling exceptional points (EPs) have unveiled intriguing chiral dynamics in photonics. However, the traditional approach based on an open manifold of Hamiltonian parameter space fails to explore trajectories that pass through an infinite boundary. Here, by mapping the full parameter space onto a closed manifold of the Riemann sphere, we introduce a framework to describe encircling-EP loops. We demonstrate that an encircling trajectory crossing the north vertex can realize near-unity asymmetric transmission. An efficient gain-free, broadband asymmetric polarization-locked device is realized by mapping the encircling path onto L-shaped silicon waveguides.

Rational design and synthesis of Oreoch-2 analogues as efficient broad-spectrum antimicrobial peptides.

In recent years, bacterial resistance has risen sharply, which seriously endangers public health due to the abuse of antibiotics and the lack of new antibiotics. Therefore, there is an urgent need for new antimicrobial agents to combat multidrug-resistant (MDR) bacterial infections. In this paper, six Oreoch-2 analogues were rationally designed and efficiently synthesized by using the truncation strategy with Oreoch-2 as the lead compound. Evaluation of these analogues against a panel of Gram-positive and Gram-negative bacteria including MDR strains was performed. Among them, ZN-5 and ZN-6 were identified to be broad-spectrum effective analogues, which were superior to their parent peptide Oreoch-2. In addition, ZN-5 and ZN-6 had good stability to the physiological environment, and much higher selectivity to bacterial cells than to mammalian cells. Time-kill kinetics and transmission electron microscope (TEM) studies suggested that these analogues were typical bactericidal agents and quickly eliminated bacteria in a bactericidal mode by disrupting bacterial cell membrane. Moreover, ZN-5 and ZN-6 could inhibit biofilm formation of Staphylococcus aureus ATCC25923. Compared with their parent peptide Oreoch-2, ZN-5 and ZN-6 not only possessed shortened peptide chains, but also showed slightly improved antibacterial activity and greatly reduced hemolysis. This indicates that they are ideal lead compounds of antimicrobial peptides, which can be developed as substitutes for traditional antibiotics.

Acridinium-conjugated aromatic heterocycles as highly potent FtsZ inhibitors: Design, synthesis, and biological evaluation.

The epidemic of multidrug resistance (MDR) is a serious threat to public health, and new classes of antibiotics with novel mechanisms of action are in critical need. We rationally designed and efficiently synthesized three series of new chemical entities with potential antibacterial activity targeting filamenting temperature-sensitive mutant Z (FtsZ). Evaluation of these compounds against a panel of Gram-positive bacteria including MDR and vancomycin-resistant Enterococcus strains indicated that most compounds showed enhanced antibacterial efficacy, comparable or even superior to the reference drugs. The newly synthesized compounds proved to be substrates of the Escherichia coli efflux pump AcrB, thus affecting the activity. Their structure-activity relationships were summarized in detail. The most potent compound 10f quickly eliminated bacteria in a bactericidal mode, with low susceptibility to induce bacterial resistance. Further mechanistic studies with the BsFtsZ protein revealed that 10f functioned as an effective FtsZ inhibitor through altering the dynamics of FtsZ self-polymerization via a stimulatory mechanism, which leads to inhibition of cell division and cell death. Besides, 10f not only displayed no obvious cytotoxicity to mammalian cells but also had a high efficacy in a murine model of bacteremia in vivo. Regarded as a whole, our findings highlight 10f as a promising new FtsZ-targeting bactericidal agent.

Extremize Optical Chiralities through Polarization Singularities.

Chiral optical effects are generally quantified along some specific incident directions of exciting waves (especially for extrinsic chiralities of achiral structures) or defined as direction-independent properties by averaging the responses among all structure orientations. Though of great significance for various applications, chirality extremization (maximized or minimized) with respect to incident directions or structure orientations has not been explored, especially in a systematic manner. In this study we examine the chiral responses of open photonic structures from perspectives of quasinormal modes and polarization singularities of their far-field radiations. The nontrivial topology of the momentum sphere secures the existence of generic singularity directions along which mode radiations are either circularly or linearly polarized. When plane waves are incident along those directions, the reciprocity ensures ideal maximization and minimization of optical chiralities, for corresponding mode radiations of circular and linear polarizations, respectively. For directions of general elliptical polarizations, we have unveiled the subtle equality of a Stokes parameter and the circular dichroism, showing that an intrinsically (geometrically) chiral structure can unexpectedly exhibit no optical chirality at all or even optical chiralities of opposite handedness for different incident directions. The framework we establish can be applied to not only finite scattering bodies but also infinite structures, encompassing both intrinsic and extrinsic optical chiralities. We have effectively merged two vibrant disciplines of chiral and singular optics, which can potentially trigger more optical chirality-singularity related interdisciplinary studies.

Microdynamic Study of Spin-Lattice Coupling Effects on Skyrmion Transport.

Skyrmion transport fundamentally determines the speed, energy consumption, and functionality of skyrmion-based spintronic devices, attracting considerable attention. Recent experimental studies found there is a migration barrier for the thermal activated transport of a skyrmion, which is speculated to be induced by the pinning effects of crystalline defects. In this Letter, we propose an alternative source of migration barrier for skyrmion transport, i.e., a local lattice distortion field due to spin-lattice coupling, which can lead to the same Arrhenius diffusion behavior in defect-free skyrmion materials. By performing spin-lattice dynamics simulations, we study the microdynamic insight into the influence of local lattice distortion field, which refreshes the mechanistic understanding on skyrmion transport.

Design, synthesis and structure-activity relationships of novel N11-, C12- and C13-substituted 15-membered homo-aza-clarithromycin derivatives against various resistant bacteria.

Bacterial infections are still the main significant problem of public health in the world, and their elimination will greatly rely on the discovery of antibacterial drugs. In the processes of our searching for novel macrolide derivatives with excellent activity against sensitive and resistant bacteria, three series of novel N11-, C12- and C13-substituted 15-membered homo-aza-clarithromycin derivatives were designed and synthesized as Series A, B and C by creatively opening the lactone ring of clarithromycin (CAM), introducing various 4-substituted phenyl-1H-1,2,3-triazole side chains at the N11, C12 or C13 position of CAM and macrolactonization. The results from their in vitro antibacterial activity demonstrated that compounds 20c, 20d and 20f displayed not only the most potent activity against S. aureus ATCC25923 with the MIC values of 0.5, 0.5 and 0.5 µg/mL, but also greatly improved activity against B. subtilis ATCC9372 with the MIC values of less than or equal to 0.25, 0.25 and 0.25 µg/mL, respectively. In particular, compound 11g exhibited the strongest antibacterial effectiveness against all the tested resistant bacterial strains and had well balanced activity with the MIC values of 4-8 µg/mL. Further study on minimum bactericidal concentration and kinetics confirmed that compound 11g possessed a bacteriostatic effect on bacterial proliferation. Moreover, the results of molecular docking revealed an potential additional binding force between compound 11g and U790 in addition to the normal binding force of macrolide skeleton, which may explain why this compound performed the most potent activity against resistant bacteria. The results of cytotoxic assay indicated that compounds 20c, 20d and 20f were non-toxic to human breast cancer MCF-7 cells at its effective antibacterial concentration.

Equine-Origin Immunoglobulin Fragments Protect Nonhuman Primates from Ebola Virus Disease.

Ebola virus (EBOV) infections result in aggressive hemorrhagic fever in humans, with fatality rates reaching 90% and with no licensed specific therapeutics to treat ill patients. Advances over the past 5 years have firmly established monoclonal antibody (MAb)-based products as the most promising therapeutics for treating EBOV infections, but production is costly and quantities are limited; therefore, MAbs are not the best candidates for mass use in the case of an epidemic. To address this need, we generated EBOV-specific polyclonal F(ab')2 fragments from horses hyperimmunized with an EBOV vaccine. The F(ab')2 was found to potently neutralize West African and Central African EBOV in vitro Treatment of nonhuman primates (NHPs) with seven doses of 100 mg/kg F(ab')2 beginning 3 or 5 days postinfection (dpi) resulted in a 100% survival rate. Notably, NHPs for which treatment was initiated at 5 dpi were already highly viremic, with observable signs of EBOV disease, which demonstrated that F(ab')2 was still effective as a therapeutic agent even in symptomatic subjects. These results show that F(ab')2 should be advanced for clinical testing in preparation for future EBOV outbreaks and epidemics.IMPORTANCE EBOV is one of the deadliest viruses to humans. It has been over 40 years since EBOV was first reported, but no cure is available. Research breakthroughs over the past 5 years have shown that MAbs constitute an effective therapy for EBOV infections. However, MAbs are expensive and difficult to produce in large amounts and therefore may only play a limited role during an epidemic. A cheaper alternative is required, especially since EBOV is endemic in several third world countries with limited medical resources. Here, we used a standard protocol to produce large amounts of antiserum F(ab')2 fragments from horses vaccinated with an EBOV vaccine, and we tested the protectiveness in monkeys. We showed that F(ab')2 was effective in 100% of monkeys even after the animals were visibly ill with EBOV disease. Thus, F(ab')2 could be a very good option for large-scale treatments of patients and should be advanced to clinical testing.

On the constraints of electromagnetic multipoles for symmetric scatterers: eigenmode analysis.

The scattering and resonant properties of optical scatterers/resonators are determined by the relative ratios among the associated multipole components, the calculation of which usually is analytically tedious and numerically complicated for complex structures. Here we identify the constraints as well as the relative relations among electromagnetic multipoles for the eigenmodes of symmetric scatterers/resonators. By reducing the symmetry properties of the vector spherical harmonic waves to those of the modified generating functions, we systematically study the required conditions for electromagnetic multipoles under several fundamental symmetry operations, i.e., 2D rotation and reflection operations and 3D proper and improper rotations. Taking a 2D scatterer with C4v as an example, we show that each irreducible representation of C4v can be assigned to corresponding electromagnetic multipoles, and consequently the constraints of the electromagnetic multipoles can be easily extracted. Such group approach can easily be extended to more complex 3D scatterers with higher symmetry group. Subsequently, we use the same procedure to map out the complete relation and constraint on the electromagnetic multipoles of a 3D scatterer imposed by D3h symmetry. Our theoretical analyses are in perfect agreements with the fullwave finite element calculations of the eigenmodes of the symmetric scatters.