Experimental Realization of Stable Exceptional Chains Protected by Non-Hermitian Latent Symmetries Unique to Mechanical Systems.

Lines of exceptional points are robust in the three-dimensional non-Hermitian parameter space without requiring any symmetry. However, when more elaborate exceptional structures are considered, the role of symmetry becomes critical. One such case is the exceptional chain (EC), which is formed by the intersection or osculation of multiple exceptional lines (ELs). In this Letter, we investigate a non-Hermitian classical mechanical system and reveal that a symmetry intrinsic to second-order dynamical equations, in combination with the source-free principle of ELs, guarantees the emergence of ECs. This symmetry can be understood as a non-Hermitian generalized latent symmetry, which is absent in prevailing formalisms rooted in first-order Schrödinger-like equations and has largely been overlooked so far. We experimentally confirm and characterize the ECs using an active mechanical oscillator system. Moreover, by measuring eigenvalue braiding around the ELs meeting at a chain point, we demonstrate the source-free principle of directed ELs that underlies the mechanism for EC formation. Our Letter not only enriches the diversity of non-Hermitian exceptional point configurations, but also highlights the new potential for non-Hermitian physics in second-order dynamical systems.

Culin5 aggravates hypoxic pulmonary hypertension by activating TRAF6/NF-κB/HIF-1α/VEGF.

Hypoxic pulmonary hypertension (HPH) lacks effective pharmacologic treatments. Microarray-based gene expression indicates the crucial role of Cullin 5 (Cul 5) in HPH. This study showed that Cul 5 was upregulated in HPH patients and a murine model of HPH. In vitro, Cul 5 promoted the angiogenesis and adhesion capacity of human pulmonary artery endothelial cells (PAECs), which could be mitigated by Cul 5 inactivation mediated by pevonedistat or NEDD8 silence. In vivo, silencing of Cul 5 in the endothelium and Cul 5 inactivation by pevonedistat could also alleviate hypoxic vascular remodeling. Mechanistic research showed that Cul 5 participated in HPH pathogenesis via the TRAF6/NF-κB/HIF-1α/VEGF pathway. Inhibition of the TRAF6/NF-κB/HIF-1α/VEGF pathway could reverse Cul 5-induced human PAEC dysfunction. These findings demonstrate that Cul 5 is an important mediator of HPH via the TRAF6/NF-κB/HIF-1α/VEGF pathway firstly, and could be considered as a potential therapeutic target in the clinical treatment of HPH.

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.

RAGE Is a Receptor for SARS-CoV-2 N Protein and Mediates N Protein-induced Acute Lung Injury.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (N-protein) increases early in body fluids during infection and has recently been identified as a direct inducer for lung injury. However, the signal mechanism of N-protein in the lung inflammatory response remains poorly understood. The goal of this study was to determine whether RAGE (receptor for advanced glycation endproducts) participated in N-protein-induced acute lung injury. The binding between N-protein and RAGE was examined via assays for protein-protein interaction. To determine the signaling mechanism in vitro, cells were treated with recombinant N-protein and assayed for the activation of the RAGE/MAPK (mitogen-activated protein kinase)/NF-ĸB pathway. RAGE deficiency mice and antagonist were used to study N-protein-induced acute lung injury in vivo. Binding between N-protein and RAGE was confirmed via flow cytometry-based binding assay, surface plasmon resonance, and ELISA. Pull-down and coimmunoprecipitation assays revealed that N-protein bound RAGE via both N-terminal and C-terminal domains. In vitro, N-protein activated the RAGE-ERK1/2-NF-ĸB signaling pathway and induced a proinflammatory response. RAGE deficiency subdued N-protein-induced proinflammatory signaling and response. In vivo, RAGE was upregulated in the BAL and lung tissue after recombinant N-protein insult. RAGE deficiency and small molecule antagonist partially protected mice from N-protein-induced acute lung injury. Our study demonstrated that RAGE is a receptor for N-protein. RAGE is partially responsible for N-protein-induced acute lung injury and has the potential to become a therapeutic target for treating coronavirus disease.

Scalar topological photonic nested meta-crystals and skyrmion surface states in the light cone continuum.

Topological photonics is rapidly expanding. However, discovering three-dimensional topological electromagnetic systems can be more challenging than electronic systems for two reasons. First, the vectorial nature of electromagnetic waves results in complicated band dispersions, and simple tight-binding-type predictions usually fail. Second, topological electromagnetic surface modes inside the light cone have very low quality factors (Q factors). Here, we propose the concept of scalar topological photonics to address these challenges. Our approach is experimentally validated by employing a nested meta-crystal configuration using connected coaxial waveguides. They exhibit scalar-wave-like band dispersions, making the search for photonic topological phases an easier task. Their surface states have skyrmion-like electric field distributions, resulting in a whole, bright surface state band inside the light cone continuum. As such, the topological surface states in our three-dimensional nested crystals can be exposed to air, making such systems well-suited for practical applications.

Non-spike and spike-specific memory T cell responses after the third dose of inactivated COVID-19 vaccine.

Background: During the COVID-19 epidemic, vaccination has become the most safe and effective way to prevent severe illness and death. Inactivated vaccines are the most widely used type of COVID-19 vaccines in the world. In contrast to spike-based mRNA/protein COVID-19 vaccines, inactivated vaccines generate antibodies and T cell responses against both spike and non-spike antigens. However, the knowledge of inactivated vaccines in inducing non-spike-specific T cell response is very limited. Methods: In this study, eighteen healthcare volunteers received a homogenous booster (third) dose of the CoronaVac vaccine at least 6 months after the second dose. CD4+ and CD8+ T cell responses against a peptide pool from wild-type (WT) non-spike proteins and spike peptide pools from WT, Delta, and Omicron SARS-CoV-2 were examined before and 1-2 weeks after the booster dose. Results: The booster dose elevated cytokine response in CD4+ and CD8+ T cells as well as expression of cytotoxic marker CD107a in CD8+ T cells in response to non-spike and spike antigens. The frequencies of cytokine-secreting non-spike-specific CD4+ and CD8+ T cells correlated well with those of spike-specific from WT, Delta, and Omicron. Activation-induced markers (AIM) assay also revealed that booster vaccination elicited non-spike-specific CD4+ and CD8+ T cell responses. In addition, booster vaccination produced similar spike-specific AIM+CD4+ and AIM+CD8+ T cell responses to WT, Delta, and Omicron, indicting strong cross-reactivity of functional cellular response between WT and variants. Furthermore, booster vaccination induced effector memory phenotypes of spike-specific and non-spike-specific CD4+ and CD8+ T cells. Conclusions: These data suggest that the booster dose of inactive vaccines broadens both non-spike-specific and spike-specific T cell responses against SARS-CoV-2.

Targeting Endothelial ENO1 (Alpha-Enolase) -PI3K-Akt-mTOR Axis Alleviates Hypoxic Pulmonary Hypertension.

BACKGROUND: It has been shown that glycolytic protein ENO1 (alpha-enolase) contributes to the pathogenesis of pulmonary hypertension through acting smooth muscle cells; however, the roles of ENO1-caused endothelial and mitochondrial dysfunctions in Group 3 pulmonary hypertension remain unexplored. METHODS: PCR array and RNA sequencing were used to screen and decipher the differential gene expression by hypoxia-treated human pulmonary artery endothelial cells. Techniques of small-interfering RNA, specific inhibitor and plasmids carrying gene of ENO1, interventions with specific inhibitor and AAV-ENO1 delivery were employed to explore the role of ENO1 in hypoxic pulmonary hypertension in vitro and in vivo, respectively. Assays for cell proliferation, angiogenesis, and adhesion were employed to analyze cell behaviors, while seahorse analysis was used to measure mitochondrial function of human pulmonary artery endothelial cells. RESULTS: PCR array data showed that ENO1 expression increased in human pulmonary artery endothelial cells exposed to hypoxia, as well as in lung tissues from patients with chronic obstructive lung disease-associated pulmonary hypertension and murine model of hypoxic pulmonary hypertension. Inhibition of ENO1 restored the hypoxia-induced endothelial dysfunction, including excessive proliferation, angiogenesis, and adhesion, while overexpression of ENO1 promotes these disorders of human pulmonary artery endothelial cells. RNA-seq showed that ENO1 targets mitochondrion-related genes and PI3K-Akt signaling pathway, which were validated in vitro and in vivo. Mice treated with ENO1 inhibitor exhibited ameliorated pulmonary hypertension and improved right ventricular failure induced by hypoxia. A reversal effect was observed in mice exposed to hypoxia and inhaled adeno-associated virus overexpressing ENO1. CONCLUSIONS: These results indicate that hypoxic pulmonary hypertension is associated with an increased level of ENO1 and that targeting ENO1 might reduce experimental hypoxic pulmonary hypertension by improving endothelial and mitochondrial dysfunction via PI3K-Akt-mTOR signaling pathway.

An investigation of the diachronic trend of dependency distance minimization in magazines and news.

The principle of minimization of dependency distance (DD) can reduce the working memory burden of language speakers, that is, reduce the cognitive burden during the communication process. This investigation demonstrated the dependency distance (based on the dependency grammar) minimization principle from a diachronic perspective in two text types of magazines and news with inspection indicators of mean dependency distance (MDD) and normalized dependency distance (NDD). This research revealed a fluctuation tendency around a certain axis concerning diachronic dependency distance variation. This research also indicated that news text balances language complexity and communication efficiency better than magazine text.

Topological near fields generated by topological structures.

The central idea of metamaterials and metaoptics is that, besides their base materials, the geometry of structures offers a broad extra dimension to explore for exotic functionalities. Here, we discover that the topology of structures fundamentally dictates the topological properties of optical fields and offers a new dimension to exploit for optical functionalities that are irrelevant to specific material constituents or structural geometries. We find that the nontrivial topology of metal structures ensures the birth of polarization singularities (PSs) in the near field with rich morphologies and intriguing spatial evolutions including merging, bifurcation, and topological transition. By mapping the PSs to non-Hermitian exceptional points and using homotopy theory, we extract the core invariant that governs the topological classification of the PSs and the conservation law that regulates their spatial evolutions. The results bridge singular optics, topological photonics, and non-Hermitian physics, with potential applications in chiral sensing, chiral quantum optics, and beyond photonics in other wave systems.

Observation of boundary induced chiral anomaly bulk states and their transport properties.

The most useful property of topological materials is perhaps the robust transport of topological edge modes, whose existence depends on bulk topological invariants. This means that we need to make volumetric changes to many atoms in the bulk to control the transport properties of the edges in a sample. We suggest here that we can do the reverse in some cases: the properties of the edge can be used to induce chiral transport phenomena in some bulk modes. Specifically, we show that a topologically trivial 2D hexagonal phononic crystal slab (waveguide) bounded by hard-wall boundaries guarantees the existence of bulk modes with chiral anomaly inside a pseudogap due to finite size effect. We experimentally observed robust valley-selected transport, complete valley state conversion, and valley focusing of the chiral anomaly bulk states (CABSs) in such phononic crystal waveguides. The same concept also applies to electromagnetics.

Topological phononics arising from fluid-solid interactions.

Nontrivial band topologies have been discovered in classical systems and hold great potential for device applications. Unlike photons, sound has fundamentally different dynamics and symmetries in fluids and solids, represented as scalar and vector fields, respectively. So far, searches for topological phononic materials have only concerned sound in either fluids or solids alone, overlooking their intricate interactions in "mixtures". Here, we report an approach for topological phononics employing such unique interplay, and demonstrate the realization of type-II nodal rings, elusive in phononics, in a simple three-dimensional phononic crystal. Type-II nodal rings, as line degeneracies in momentum space with exotic properties from strong tilting, are directly observed through ultrasonic near-field scanning. Strongly tilted drumhead surface states, the hallmark phenomena, are also experimentally demonstrated. This phononic approach opens a door to explore topological physics in classical systems, which is easy to implement that can be used for designing high-performance acoustic devices.

Photonic Z_{2} Topological Anderson Insulators.

That disorder can induce nontrivial topology is a surprising discovery in topological physics. As a typical example, Chern topological Anderson insulators (TAIs) have been realized in photonic systems, where the topological phases exist without symmetry protection. In this Letter, by taking transverse magnetic and transverse electric polarizations as pseudospin degrees of freedom, we theoretically propose a scheme to realize disorder-induced symmetry-protected topological phase transitions in two-dimensional photonic crystals with a combined time-reversal, mirror, and duality symmetry T_{f}=TM_{z}D. In particular, we demonstrate that the disorder-induced symmetry-protected topological phase persists even without pseudospin conservation, thereby realizing a photonic Z_{2} TAI, in contrast to a Z-classified quantum spin Hall (QSH) TAI with decoupled spins. By formulating a new scattering approach, we show that the topology of both the QSH and Z_{2} TAIs can be manifested by the accumulated spin rotations of the reflected waves from the photonic crystals. Using a transmission structure, we also illustrate the trivialization of a disordered QSH phase with an even integer topological index caused by spin coupling.

Straight Photonic Nodal Lines with Quadrupole Berry Curvature Distribution and Superimaging "Fermi Arcs".

In periodic systems, nodal lines are loops in the three-dimensional momentum space with each point on them representing a band degeneracy. Nodal lines exhibit rich topological features, as they can take various configurations such as rings, links, chains, and knots. These line nodes are generally protected by mirror or PT symmetry and frequently accompanied by drumhead surface states. Here, we propose and demonstrate a novel type of photonic straight nodal lines in a D_{2D} metacrystal, which are protected by an unusual rotoinversion time (roto-PT) symmetry. These nodal lines are located at the central axis and hinges of the Brillouin zone. They appear as quadrupole sources of Berry curvature flux in contrast to the Weyl points, which are monopoles. Interestingly, topological surface states exist at all three cutting surfaces, as guaranteed by π-quantized Zak phases along all three directions. As frequency changes, the surface state equifrequency contours evolve from closed to open and become straight lines at a critical transition frequency, at which diffractionless surface wave propagations are experimentally demonstrated, paving the way toward development of superimaging topological devices.

Efficacy of low-dose corticosteroids in patients with acute respiratory distress syndrome: a prospective observational study.

Background: There is still no agreement on whether corticosteroids can reduce mortality in patients with acute respiratory distress syndrome (ARDS). The aim of this study was to investigate the efficacy of low-dose corticosteroid administration in patients with ARDS. Methods: A prospective observational study of patients with ARDS in 17 hospitals in China was performed between March 2016 and February 2018. Propensity score matching was performed to adjust for differences in baseline characteristics between different groups. The effects of corticosteroids were assessed by using the Kaplan-Meier method and a multivariate Cox regression. Results: A total of 527 ARDS patients were enrolled in the study. Sixty-five patients (12.3%) were administered low-dose (methylprednisolone ≤1 mg·kg-1·d-1) corticosteroids. The median dose was equivalent to 0.67 (0.57-0.81) mg/kg methylprednisolone for a median duration of 10 days. The control group included 224 patients (42.5%) who had never receive corticosteroids. In the matched sample, the hospital mortality rates in the low-dose (n=40) and control groups (n=80) were 27.5% and 42.5% (P=0.110), respectively. The length of hospital stay was significantly longer in the low-dose corticosteroid group than in the control group (24.0 vs. 17.0, P=0.002), and the multivariate Cox regression analysis suggested that the low-dose group had a significantly lower risk of death than the control group (HR: 0.48; 95% CI: 0.24-0.97; P=0.040). Conclusions: The administration of low-dose corticosteroids may reduce mortality in patients with ARDS.

Experimental Observation of Non-Abelian Earring Nodal Links in Phononic Crystals.

Nodal lines are symmetry-protected one-dimensional band degeneracies in momentum space, which can appear in numerous topological configurations such as nodal rings, chains, links, and knots. Very recently, non-Abelian topological physics have been proposed in space-time inversion (PT) symmetric systems. One of the most special configurations in such systems is the earring nodal link, composing of a nodal chain linking with an isolated nodal line. Such earring nodal links have not been observed in real systems. We designed phononic crystals with earring nodal links, and experimentally observed two different kinds of earring nodal links by measuring the band structures. We found that the order of the nodal chain and line can be switched after band inversion but their link cannot be severed. Our Letter provides experimental evidence for phenomena unique to non-Abelian band topology and our acoustic system provides a convenient platform for studying the new materials carrying non-Abelian charges.

[Identification of Weak D Type 1 in Rh Blood Group System and Discussion of Transfusion Strategy].

OBJECTIVE: To investigate the molecular mechanism of one patient with abnormal serological phenotype in RhD and discuss the transfusion strategy. METHODS: The RhD variant sample was screened from a patient with IgM type anti-D antibody and further determined by three different sources of anti-D antibodies. Ten exons and the adjacent introns of the RHD gene were amplified, purified and sequenced. RhCE phenotypes and RHCE genotypes were detected. RESULTS: The patient with Rh variant showed abnormal results of serological tests. The RHD gene sequence analysis showed that the RHD*01W.01 with a variation (c.809T>G, p.Val270Gly) in exon 6 of the RHD gene was found in the patient. The RhCE phenotype was CcEe. The genotyping results of RHCE were consistent with the serological typing results. CONCLUSION: The Rh variant of the patient is RHD*01W.01, these findings indicate that RhD variants should be analyzed by molecular assays for the sake of safe transfusion.

Multiproxy probing of anthropogenic influences on the different components of dissolved organic matter in coastal rainwater.

In an environment that is tightly linked to humankind, how anthropogenic activity affects the quality and quantity of dissolved organic matter (DOM) in atmospheric depositions is not well understood. In this study, dissolved organic carbon (DOC), UV-vis spectra combined with molecular markers, including formic acid (FA), acetic acid (AA) and dissolved black carbon (DBC), were applied to track the temporal variation and influential factors of rainwater DOM at a coastal site. The ranges of DOC, light absorption at 254 nm (a254), FA, AA and DBC were 23.2-471 µmol L-1, 0.16-10.6 m-1, 0.12-23.5 µmol L-1, 0.44-37.8 µmol L-1 and 0.02-4.8 µmol L-1, respectively. The negative correlations between DOC, a254, AA and precipitation amount revealed a dilution effect. The concentrations of all measured DOM components were statistically different among different seasons with the highest value in spring. Higher DOM concentrations also occurred in the rain with backward trajectories influenced by the land. Compared to the nearby riverine DOM, the DOC-specific UV absorbance (SUVA254) of rainwater was lower, suggesting lower aromaticity of rainwater DOM. Significant correlations among different DOM components suggest that they shared similar sources or were affected by the same processes, while the significant correlations with anions (SO42-, F- and NO3-) and the ratio of FA to AA all suggested that the direct emission and secondary production from anthropogenic emissions (fossil fuel burning, biomass and biofuel burning) played important roles in regulating the level of DOM concentration in rainwater. Correlations with environmental variables (PM2.5, CO and NO2) further confirmed the input from anthropogenic activities. Furthermore, the monthly wet atmospheric deposition fluxes of DOM components (except DBC) can be successfully simulated by monthly precipitation and monthly average values of PM2.5 and NO2. Future studies should examine how atmospheric deposition affects the biogeochemical cycles in coastal regions.

Observation of Non-Abelian Charged Nodes Linking Nonadjacent Gaps.

Nodal links are special configurations of band degeneracies in the momentum space, where nodal line branches encircle each other. In PT symmetric systems, nodal lines can be topologically characterized using the eigenvector frame rotations along an encircling loop and the linking structure can be described with non-Abelian frame charges involving adjacent bands. While the commutation rules between the frame charges are well established, the underlying relationship between distant band gap closing nodes remains to be explored. In this Letter, we present a photonic multiple nodal links system, where the nodal lines of nonadjacent bands are investigated with symmetry constraints on frame charges. Through an orthogonal nodal chain, the nodal line from the lower two bands predicts the existence of nodal lines formed between the higher bands. We designed and fabricated a metamaterial, with which the multiple nodal links and the topological connection between nonadjacent nodal lines are experimentally demonstrated.

[Different Subtypes Caused by c.721C>T Substitution in the Exon 7 of ABO Gene].

OBJECTIVE: To analyze the different subtypes caused by c.721C>T substitution in the exon 7 of the ABO gene, and to investigate the related molecular mechanism of different antigens expression. METHODS: ABO subtypes in 7 samples were identified by standard serological methods. The exons 6, 7, and adjacent intron of ABO gene were amplified by Polymerase Chain Reaction (PCR), and the PCR products were analyzed by direct DNA sequencing and cloning sequencing. RESULTS: ABO subtypes phenotypes were AW (1 case), BW (3 cases), ABW (2 cases), A2 or Aint (1 case). The result showed that the 7th exon of ABO gene was c.721C>T variety based on A1.02, B1.01, and O.01.02; the alleles were AW.43（1 case）, BW.03（5 cases） and O.01.07（1 case）, ABO genotypes were ABO*AW.43/O.01.02 (1 case) , ABO*BW.03/O.01.02 (3 cases), ABO*A1.02/BW.03 (2 cases), and ABO*A2.05/O.01.07 (1 case). CONCLUSION: c.721C>T substitution in the ABO gene causes p.Arg241Trp exchange resulting in the decreasing of GTA or GTB activities and weaker antigen expression. O.01.07 is a null allele which cannot form a functional catalytic enzyme has no effect on A2 subtype antigen expression.

Four-band non-Abelian topological insulator and its experimental realization.

Very recently, increasing attention has been focused on non-Abelian topological charges, e.g., the quaternion group Q8. Different from Abelian topological band insulators, these systems involve multiple entangled bulk bandgaps and support nontrivial edge states that manifest the non-Abelian topological features. Furthermore, a system with an even or odd number of bands will exhibit a significant difference in non-Abelian topological classification. To date, there has been scant research investigating even-band non-Abelian topological insulators. Here, we both theoretically explore and experimentally realize a four-band PT (inversion and time-reversal) symmetric system, where two new classes of topological charges as well as edge states are comprehensively studied. We illustrate their difference in the four-dimensional (4D) rotation sense on the stereographically projected Clifford tori. We show the evolution of the bulk topology by extending the 1D Hamiltonian onto a 2D plane and provide the accompanying edge state distributions following an analytical method. Our work presents an exhaustive study of four-band non-Abelian topological insulators and paves the way towards other even-band systems.