Topological state transitions of skyrmionic beams under focusing configurations.

The recent emerging appearance of optical analogs of magnetic quasiparticles, i.e., optical skyrmions constructed via spin, field, and Stokes vectors, has garnered substantial interest from deep-subwavelength imaging and quantum entanglement. Here, we investigate systematically the topological state transitions of skyrmionic beams constructed by the Stokes vectors in the focusing configuration. We theoretically demonstrated that in the weak focusing, the skyrmion topological number is protected. Whereas, in the tight focusing, a unique topological transformation with skyrmion number variation is exhibited for the optical skyrmion, anti-skyrmion, and 2nd-order skyrmion structures. The significant difference between the topological state transitions of these two cases originates from the transformation from the paraxial optical system to the nonparaxial optical system, and the approximate two-dimensional polarization structure to the three-dimensional polarization structure. The results provide new insights into the topological state transitions in topological structures, which promote applications in information processing, data storage, and free-space optical communications.

Ischemia-Selective Cardioprotection by Malonate for Ischemia/Reperfusion Injury.

BACKGROUND: Inhibiting SDH (succinate dehydrogenase), with the competitive inhibitor malonate, has shown promise in ameliorating ischemia/reperfusion injury. However, key for translation to the clinic is understanding the mechanism of malonate entry into cells to enable inhibition of SDH, its mitochondrial target, as malonate itself poorly permeates cellular membranes. The possibility of malonate selectively entering the at-risk heart tissue on reperfusion, however, remains unexplored. METHODS: C57BL/6J mice, C2C12 and H9c2 myoblasts, and HeLa cells were used to elucidate the mechanism of selective malonate uptake into the ischemic heart upon reperfusion. Cells were treated with malonate while varying pH or together with transport inhibitors. Mouse hearts were either perfused ex vivo (Langendorff) or subjected to in vivo left anterior descending coronary artery ligation as models of ischemia/reperfusion injury. Succinate and malonate levels were assessed by liquid chromatography-tandem mass spectrometry LC-MS/MS, in vivo by mass spectrometry imaging, and infarct size by TTC (2,3,5-triphenyl-2H-tetrazolium chloride) staining. RESULTS: Malonate was robustly protective against cardiac ischemia/reperfusion injury, but only if administered at reperfusion and not when infused before ischemia. The extent of malonate uptake into the heart was proportional to the duration of ischemia. Malonate entry into cardiomyocytes in vivo and in vitro was dramatically increased at the low pH (≈6.5) associated with ischemia. This increased uptake of malonate was blocked by selective inhibition of MCT1 (monocarboxylate transporter 1). Reperfusion of the ischemic heart region with malonate led to selective SDH inhibition in the at-risk region. Acid-formulation greatly enhances the cardioprotective potency of malonate. CONCLUSIONS: Cardioprotection by malonate is dependent on its entry into cardiomyocytes. This is facilitated by the local decrease in pH that occurs during ischemia, leading to its selective uptake upon reperfusion into the at-risk tissue, via MCT1. Thus, malonate's preferential uptake in reperfused tissue means it is an at-risk tissue-selective drug that protects against cardiac ischemia/reperfusion injury.

Stem cell antigen-1+cell-derived fibroblasts are crucial for cardiac fibrosis during heart failure.

AIMS: Mesenchymal stem cells (MSCs) present in the heart cannot differentiate into cardiomyocytes, but may play a role in pathological conditions. Therefore, the aim of this study was to scrutinise the role and mechanism of MSC differentiation in vivo during heart failure. METHODS AND RESULTS: We performed single-cell RNA sequencing of total non-cardiomyocytes from murine and adult human hearts. By analysing the transcriptomes of single cells, we illustrated the dynamics of the cell landscape during the progression of heart hypertrophy, including those of stem cell antigen-1 (Sca1)+ stem/progenitor cells and fibroblasts. By combining genetic lineage tracing and bone marrow transplantation models, we demonstrated that non-bone marrow-derived Sca1+ cells give rise to fibroblasts. Interestingly, partial depletion of Sca1+ cells alleviated the severity of myocardial fibrosis and led to a significant improvement in cardiac function in Sca1-CreERT2;Rosa26-eGFP-DTA mice. Similar non-cardiomyocyte cell composition and heterogeneity were observed in human patients with heart failure. Mechanistically, our study revealed that Sca1+ cells can transform into fibroblasts and affect the severity of fibrosis through the Wnt4-Pdgfra pathway. CONCLUSIONS: Our study describes the cellular landscape of hypertrophic hearts and reveals that fibroblasts derived from Sca1+ cells with a non-bone marrow source largely account for cardiac fibrosis. These findings provide novel insights into the pathogenesis of cardiac fibrosis and have potential therapeutic implications for heart failure. Non-bone marrow-derived Sca1+ cells differentiate into fibroblasts involved in cardiac fibrosis via Wnt4-PDGFRα pathway.

Transverse spin dynamics in structured electromagnetic guided waves.

Spin-momentum locking, a manifestation of topological properties that governs the behavior of surface states, was studied intensively in condensed-matter physics and optics, resulting in the discovery of topological insulators and related effects and their photonic counterparts. In addition to spin, optical waves may have complex structure of vector fields associated with orbital angular momentum or nonuniform intensity variations. Here, we derive a set of spin-momentum equations which describes the relationship between the spin and orbital properties of arbitrary complex electromagnetic guided modes. The predicted photonic spin dynamics is experimentally verified with four kinds of nondiffracting surface structured waves. In contrast to the one-dimensional uniform spin of a guided plane wave, a two-dimensional chiral spin swirl is observed for structured guided modes. The proposed framework opens up opportunities for designing the spin structure and topological properties of electromagnetic waves with practical importance in spin optics, topological photonics, metrology and quantum technologies and may be used to extend the spin-dynamics concepts to fluid, acoustic, and gravitational waves.

Multilineage contribution of CD34+ cells in cardiac remodeling after ischemia/reperfusion injury.

The ambiguous results of multiple CD34+ cell-based therapeutic trials for patients with heart disease have halted the large-scale application of stem/progenitor cell treatment. This study aimed to delineate the biological functions of heterogenous CD34+ cell populations and investigate the net effect of CD34+ cell intervention on cardiac remodeling. We confirmed, by combining single-cell RNA sequencing on human and mouse ischemic hearts and an inducible Cd34 lineage-tracing mouse model, that Cd34+ cells mainly contributed to the commitment of mesenchymal cells, endothelial cells (ECs), and monocytes/macrophages during heart remodeling with distinct pathological functions. The Cd34+-lineage-activated mesenchymal cells were responsible for cardiac fibrosis, while CD34+Sca-1high was an active precursor and intercellular player that facilitated Cd34+-lineage angiogenic EC-induced postinjury vessel development. We found through bone marrow transplantation that bone marrow-derived CD34+ cells only accounted for inflammatory response. We confirmed using a Cd34-CreERT2; R26-DTA mouse model that the depletion of Cd34+ cells could alleviate the severity of ventricular fibrosis after ischemia/reperfusion (I/R) injury with improved cardiac function. This study provided a transcriptional and cellular landscape of CD34+ cells in normal and ischemic hearts and illustrated that the heterogeneous population of Cd34+ cell-derived cells served as crucial contributors to cardiac remodeling and function after the I/R injury, with their capacity to generate diverse cellular lineages.

Metastability of photonic spin meron lattices in the presence of perturbed spin-orbit coupling.

Photonic skyrmions and merons are topological quasiparticles characterized by nontrivial electromagnetic textures, which have received increasing research attention recently, providing novel degree of freedom to manipulate light-matter interactions and exhibiting excellent potential in deep-subwavelength imaging and nanometrology. Here, the topological stability of photonic spin meron lattices, which indicates the invariance of skyrmion number and robustness of spin texture under a continuous deformation of the field configuration, is demonstrated by inducing a perturbation to break the C4 symmetry in the presence spin-orbit coupling in an optical field. We revealed that amplitude perturbation would result in an amplitude-dependent shift of spin center, while phase perturbation leads to the deformation of domain walls, manifesting the metastability of photonic meron. Such spin topology is verified through the interference of plasmonic vortices with a broken rotational symmetry. The results provide new insights on optical topological quasiparticles, which may pave the way towards applications in topological photonics, optical information storage and transfer.

Nonbone Marrow CD34+ Cells Are Crucial for Endothelial Repair of Injured Artery.

[Figure: see text].

CD34+ cell atlas of main organs implicates its impact on fibrosis.

RATIONALE: CD34+ cells are believed being progenitors that may be used to treat cardiovascular disease. However, the exact identity and the role of CD34+ cells in physiological and pathological conditions remain unclear. METHODS: We performed single-cell RNA sequencing analysis to provide a cell atlas of normal tissue/organ and pathological conditions. Furthermore, a genetic lineage tracing mouse model was used to investigate the role of CD34+ cells in angiogenesis and organ fibrosis. RESULTS: Single-cell RNA sequencing analysis revealed a heterogeneous population of CD34+ cells in both physiological and pathological conditions. Using a genetic lineage tracing mouse model, we showed that CD34+ cells not only acquired endothelial cell fate involved in angiogenesis, but also, CD34+ cells expressing Pi16 may transform into myofibroblast and thus participate in organ fibrosis. CONCLUSION: A heterogeneous CD34+ cells serve as a contributor not only to endothelial regeneration but also a wound healing response that may provide therapeutic insights into fibrosis.

Intrinsic Spin-Momentum Dynamics of Surface Electromagnetic Waves in Dispersive Interfaces.

Intrinsic spin-momentum locking is an inherent property of surface electromagnetic fields and its study has led to the discovery of phenomena such as unidirectional guided waves and photonic spin lattices. Previously, dispersion was ignored in spin-momentum locking, resulting in anomalies contradicting the apparent physical reality. Here, we formulate four dispersive spin-momentum equations, revealing in theory that transverse spin is locked with kinetic momentum. Moreover, in dispersive metal or magnetic materials spin-momentum locking obeys the left-hand screw rule. In addition to dispersion, structural features can affect substantially this locking. Remarkably, an extraordinary spin originating from coupling polarization ellipticities is uncovered that depends on the symmetry of the field modes. We further identify the properties of this spin-momentum locking with diverse photonic topological lattices by engineering their rotational symmetry akin to that in solid-state physics. The concept of spin-momentum locking based on photon flow properties translates easily to other classical wave fields.

The AIM2 inflammasome: A novel biomarker and target in cardiovascular disease.

Absent in melanoma 2 (AIM2) is a cytoplasmic sensor that recognises the double-strand DNA. AIM2 inflammasome is a protein platform in the cell that initiates innate immune responses by cleaving pro-caspase-1 and converting IL-1ß and IL-18 to their mature forms. Additionally, AIM2 inflammasome promotes pyroptosis by converting Gasdermin-D (GSDMD) to GSDMD-N fragments. An increasing number of studies have indicated the important and decisive roles of the AIM2 inflammasome, IL-1ß, and pyroptosis in cardiovascular diseases, such as coronary atherosclerosis, myocardial infarction, ischaemia/reperfusion injury, heart failure, aortic aneurysm and ischaemic stroke. Here, we review the molecular mechanism of the activation and effect of the AIM2 inflammasome in cardiovascular disease, revealing new insights into pathogenic factors that may be targeted to treat cardiovascular disease and related dysfunctions.

Stem/Progenitor Cells and Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by endothelial dysfunction and vascular remodeling. Despite significant advancement in our understanding of the pathogenesis of PAH in recent years, treatment options for PAH are limited and their prognosis remains poor. PAH is now seen as a severe pulmonary arterial vasculopathy with structural changes driven by excessive vascular proliferation and inflammation. Perturbations of a number of cellular and molecular mechanisms have been described, including pathways involving growth factors, cytokines, metabolic signaling, elastases, and proteases, underscoring the complexity of the disease pathogenesis. Interestingly, emerging evidence suggests that stem/progenitor cells may have an impact on disease development and therapy. In preclinical studies, stem/progenitor cells displayed an ability to promote endothelial repair of dysfunctional arteries and induce neovascularization. The stem cell-based therapy for PAH are now under active investigation. This review article will briefly summarize the updates in the research field, with a special focus on the contribution of stem/progenitor cells to lesion formation via influencing vascular cell functions and highlight the potential clinical application of stem/progenitor cell therapy to PAH.

Photonic Spin Lattices: Symmetry Constraints for Skyrmion and Meron Topologies.

Symmetry and topology govern many electronic, magnetic, and photonic phenomena in condensed matter physics and optics, resulting in counterintuitive skyrmion, meron, and other phenomena important for modern technologies. Here we demonstrate photonic spin lattices as a new topological construct governed by the spin-orbit coupling in an optical field. The symmetry of the electromagnetic field in the presence of the spin-orbit interaction may result in only two types of photonic spin lattices: either hexagonal spin-skyrmion or square spin-meron lattices. We show that these spin structures correspond to the lowest energy of the electromagnetic field configuration, therefore, energetically stable. We further show that in the absence of spin-orbit coupling these spin topologies are degenerated in dynamic field skyrmions, unifying the description of electromagnetic field topologies. The results provide a new understanding of electromagnetic field topology and its transformations as well as new opportunities for applications in quantum technologies, spin optics, and topological photonics.

Surface plasmon coupled nano-probe for near field scanning optical microscopy.

Near-field scanning optical microscopy (NSOM) is a powerful tool for study of the nanoscale information of objects by measuring their near-field electric field distributions. The near-field probe, which determines NSOM system performance, can be either a scattering-type or an aperture-type. Both types have strengths and weaknesses. Here we propose and study a surface plasmon-coupled type nano-probe, which works as a hybrid scheme and could potentially combine the advantages of the two NSOM probe types. The key element of the proposed probe is a nanoparticle-on-film structure designed on a tapered fiber tip. On the one hand, the probe can yield the signals scattered in the near field by a nanoparticle with a scattering mechanism; on the other hand, the scattered signals can be transmitted by the metal film and coupled into the fiber via surface plasmon coupled emission, thus providing a collection mode similar to an aperture-type NSOM. This will lead to signal enhancement, while greatly suppressing background noise. This surface plasmon-coupled nano-probe thus has great potential for near-field optical microscopy applications.

Selective magnetic responses of silicon nanoparticles modulated by waveguide structures.

High-refractive-index nanoparticles (NPs), such as silicon NPs, were considered as effective carriers in their response to a magnetic field at optical frequencies. Such NPs play an important role in many state-of-the-art technologies in nano-optics. Although the resonance properties of these NPs when varying their structural parameters have been studied intensely in the past few years, their interaction with the underlying substrate has seldom been discussed, in particular, when the substrate is a waveguide structure that significantly modulates the optical responses of the NPs. We proposed and studied a selective magnetic coupling system comprising a Si-NP on a metal-dielectric waveguide (MDW). The MDW structure supports either a transverse electric (TE) or a transverse magnetic (TM) mode that induces a large polarization dependence in the magnetic resonance. A new manifestation of the optical spin Hall effect was demonstrated in which a vertical rotating magnetic dipole excites a TE-type waveguide mode with a specific unidirectional emission. Making use of this polarization response, we developed a scanning imaging system that can selectively map the transverse or longitudinal magnetic field component of a focused beam depending on the type of MDW used in the system. This selective magnetic resonance coupling system is expected to be valuable for studying the fundamental interactions between the magnetic field and matter and for developing related nano-applications.

Reconfigurable dielectric metasurface for active wavefront modulation based on a phase-change material metamolecule design.

Metasurfaces, the promising artificial micro-nano structures with the ability to manipulate the wavefront of light, have been widely studied and reported in recent years. However, dynamic control of the wavefront using dielectric metasurfaces remains a great challenge. Here, unlike the previously reported reconfigurable metasurfaces that offer only binary functions or limited switchable states, we propose and numerically demonstrate an active dielectric metasurface with the metamolecule unit-cell design that enables full-range phase or amplitude tuning in the telecommunications band using the phase-change material Ge2Sb2Se4Te1 (GSST). Selective control of the phase transition of each GSST nanopillar in the metamolecule allows multi-level modulation of the phase and amplitude of the light to be achieved. The functionalities of the structure are validated through the generation of optical vortices, phase-only hologram, and pure amplitude modulation. Benefiting from its dynamic wavefront control capability, the proposed metasurface offers major potential for use in future applications including complex beam steering, optical communications, 3D holograms, and displays.

Hypoxia exacerbates cardiomyocyte injury via upregulation of Wnt3a and inhibition of Sirt3.

Ischemic injury is a major cause of several cardiovascular diseases, such as myocardial infarction, cardiac hypertrophy, and ventricular remodeling. Using an in vitro hypoxia model to mimic ischemia, we found that hypoxia stimulated Wnt3a expression. A mechanistic study showed that hypoxia-inducible factor 1α (HIF-1α) was directly recruited to the Wnt3a promoter. Wnt3a overexpression significantly decreased cell viability, promoted the generation of apoptotic cells, and enhanced hypoxia-induced injury in neonatal rat cardiomyocytes. This was partially through the upregulation of Caspase-3 mRNA levels and cleaved PARP-1 protein levels. In addition, we observed that Wnt3a exacerbated hypoxia-induced mitochondrial dysfunction and cytosolic release of cytochrome C. Furthermore, we found that Sirt3, a mitochondrial NAD+-dependent deacetylase that modulates mitochondrial metabolism and homeostasis, was negatively regulated by Wnt3a. Conversely, Sirt3 overexpression repressed Wnt3a expression and ameliorated the hypoxia-induced mitochondrial dysfunction. Overall, our findings suggest that the hypoxia-Wnt3a-Sirt3 regulatory axis might be a potential target for cell protection in cardiac ischemia and hypoxia.

Development of haemagglutination assay for titration of porcine circovirus type 2.

Porcine circovirus type 2 (PCV2) was one of the most economically important viral pathogens in all the swine-producing countries and often resulted in tremendous economic losses for the swine industry. As PCV2 could not cause cytopathogenic effects while propagated in infected cells, many complicated experiments should be performed to titrate its virus titer. In this study we developed a simple and effective hemagglutination assay for titration of virus titer of PCV2. To develop the hemagglutination assay, a recombinant bispecific nanobody (BsNb) against PCV2 and chicken red blood cells (cRBCs) was constructed based on two nanobodies (NbPCV11 and NbRBC48) which were selected from the non-immunized nanobody library, respectively. The hemagglutination assay was used to titrate the virus titer of PCV2 propagated in cell culture by simple naked-eye observation within 30 min, with the detection limit of 104.09 tissue culture infective dose 50 (TCID50)/mL, excellent specificity and reproducibility. Therefore, the hemagglutination assay had potential to be a rapid, reliable, cost-effective, user-friendly qualitative and semi-quantitative tool for titration of virus titer of PCV2 during the vaccine manufacturing process.

A flagellin-adjuvanted inactivated porcine epidemic diarrhea virus (PEDV) vaccine provides enhanced immune protection against PEDV challenge in piglets.

Since late 2010, outbreaks of porcine epidemic diarrhea (PED) have been reported in the swine industry in China. A variant PEDV strain that differs from strain CV777 causes prevalent PEDV infections which commercial vaccines based on CV777 cannot provide complete protection. In this study, we designed a new vaccine based on the epidemic PEDV strain AH2012/12, adjuvanted with flagellin, a mucosal adjuvant that induces mucosal and systemic production of IgA. Three groups of pregnant sows were immunized twice, with a 14-day interval, with PEDV adjuvanted with flagellin, PEDV alone, or PBS before farrowing, and newborn piglets from each group were selected and challenged with PEDV. Immunization with this vaccine elicited high levels of IgG, IgA, and neutralizing antibodies in the serum and colostrum of sows, and newborn piglets were protected against PEDV while suckling. This study should guide the prevention and control strategies for PEDV infection, thereby reducing the losses associated with this virus.

The critical role of the zinc transporter Zip2 (SLC39A2) in ischemia/reperfusion injury in mouse hearts.

Although zinc homeostasis has been demonstrated to play a role in myocardial ischemia/reperfusion (I/R) injury, the roles of zinc transporters that are critical for zinc homeostasis in I/R injury are poorly understood. The purpose of this study was to test if Zip2, an important zinc importer, plays a role in I/R injury in mouse hearts and explore the mechanism by which Zip2 expression is regulated. Zip2 expression was increased at reperfusion in in vivo mouse hearts, an effect that was abolished by ZnCl2, indicating Zip2's attempt to compensate for zinc loss at reperfusion. Further studies showed that upregulation of Zip2 expression was reversed by either pharmacological or genetic inhibition of signal transducers and activators of transcription 3 (STAT3), whereas STAT3 overexpression increased Zip2 expression, indicating that STAT3 accounts for Zip2 upregulation. In support, reperfusion enhanced STAT3 phosphorylation (Tyr705), which was blocked by ZnCl2, implying that STAT3 is activated in response to zinc loss. To determine the role of Zip2 in I/R injury, we assessed I/R injury by genetically disrupting Zip2 expression. Knockout of Zip2 genes (Zip2+/- and Zip2-/-) exacerbated I/R injury by increasing infarct size as well as the serum LDH, troponin I (cTnI), and CK-MB activities. In contrast, delivery of Zip2 genes reduced I/R injury. Delivery of STAT3 genes increased STAT3 phosphorylation and reduced I/R injury. However, delivery of the dominant negative STAT3 mutant did not reduce I/R injury. Moreover, delivery of STAT3 genes failed to reduce I/R injury in Zip2-/- mice. Zip2 upregulated upon reperfusion via STAT3 is cardioprotective and this upregulation may serve as an important intrinsic protective mechanism by which the heart is resistant to I/R injury. The factors involved in the zinc homeostasis (zinc and Zip2) are responsible STAT3 activation and its subsequent cardioprotective action.

Low-loss metal-dielectric waveguide mode enabled structured illumination microscopy with 0.18λ0 resolution.

Structured illumination microscopy (SIM) is a powerful super-resolved imaging technique which enables to perform fast and in vivo imaging of bio-samples. In order to achieve a better resolution of a SIM system, evanescent waves with larger in-plane wave-vector are preferred for SIM, among which the total internal reflection (TIRF-SIM) and the plasmonic SIM (pSIM) configurations are widely studied. Here, we demonstrated a metal-dielectric waveguide (MDW) based SIM system - termed as MDW-SIM, which can achieve a good compromise between TIRF-SIM and pSIM. The MDW can support a low-loss waveguide mode at an aqueous environment, with an evanescent tail existing above the water/dielectric interface for SIM. A proof-of-concept imaging experiment was performed on fluorescent beads, where a spatial resolution of 86nm was achieved at a 473nm illumination wavelength and a 1.45 numerical aperture objective lens. The proposed MDW-SIM has a great potential for the bio-imaging applications.