Sleep-disordered breathing and nocturnal hypoxemia in chronic thromboembolic pulmonary disease.

BACKGROUND AND AIMS: Sleep-disordered breathing (SDB) and nocturnal hypoxemia were known to be present in patients with chronic thromboembolic pulmonary hypertension (CTEPH), but the difference between SDB and nocturnal hypoxemia in patients who have chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) at rest remains unknown. METHODS: Patients who had CTEPH (n = 80) or CTEPD without PH (n = 40) and who had undergone sleep studies from July 2020 to October 2022 at Shanghai Pulmonary Hospital were enrolled. Nocturnal mean SpO2 (Mean SpO2) <90% was defined as nocturnal hypoxemia, and the percentage of time with a saturation below 90% (T90%) exceeding 10% was used to evaluate the severity of nocturnal hypoxemia. Logistic and linear regression analyses were performed to investigate the difference and potential predictor of SDB or nocturnal hypoxemia between CTEPH and CTEPD without PH. RESULTS: SDB was similarly prevalent in CTEPH and CTEPD without PH (P = 0.104), both characterised by obstructive sleep apnoea (OSA). Twenty-two patients with CTEPH were diagnosed with nocturnal hypoxemia, whereas only three were diagnosed with CTEPD without PH (P = 0.021). T90% was positively associated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance in patients with CTEPH and CTEPD without PH (P < 0.001); T90% was also negatively related to cardiac output in these patients. Single-breath carbon monoxide diffusing capacity, sex and mPAP were all correlated with nocturnal hypoxemia in CTEPH and CTEPD without PH (all P < 0.05). CONCLUSION: Nocturnal hypoxemia was worse in CTEPD with PH; T90%, but not SDB, was independently correlated with the hemodynamics in CTEPD with or without PH.

Resolvin D2/GPR18 signaling enhances monocytic myeloid-derived suppressor cell function to mitigate abdominal aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) formation is a chronic vascular pathology characterized by inflammation, leukocyte infiltration and vascular remodeling. The aim of this study was to delineate the protective role of Resolvin D2 (RvD2), a bioactive isoform of specialized proresolving lipid mediators, via G-protein coupled receptor 18 (GPR18) receptor signaling in attenuating AAAs. Importantly, RvD2 and GPR18 levels were significantly decreased in aortic tissue of AAA patients compared with controls. Furthermore, using an established murine model of AAA in C57BL/6 (WT) mice, we observed that treatment with RvD2 significantly attenuated aortic diameter, pro-inflammatory cytokine production, immune cell infiltration (neutrophils and macrophages), elastic fiber disruption and increased smooth muscle cell α-actin expression as well as increased TGF-ß2 and IL-10 expressions compared to untreated mice. Moreover, the RvD2-mediated protection from vascular remodeling and AAA formation was blocked when mice were previously treated with siRNA for GPR18 signifying the importance of RvD2/GPR18 signaling in vascular inflammation. Mechanistically, RvD2-mediated protection significantly enhanced infiltration and activation of monocytic myeloid-derived suppressor cells (M-MDSCs) by increasing TGF-ß2 and IL-10 secretions that mitigated smooth muscle cell activation in a GPR18-dependent manner to attenuate aortic inflammation and vascular remodeling via this intercellular crosstalk. Collectively, this study demonstrates RvD2 treatment induces an expansion of myeloid-lineage committed progenitors, such as M-MDSCs, and activates GPR18-dependent signaling to enhance TGF-ß2 and IL-10 secretion that contributes to resolution of aortic inflammation and remodeling during AAA formation.

Evaluating the efficacy and safety of oral triple sequential combination therapy for treating patients with pulmonary arterial hypertension: A multicenter retrospective study.

This study aimed to evaluate the effectiveness and safety of an oral sequential triple combination therapy with selexipag after dual combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5I)/riociguat in pulmonary arterial hypertension (PAH) patients. A total of 192 PAH patients from 10 centers had received oral sequential selexipag therapy after being on dual-combination therapy with ERA and PDE5i/riociguat for a minimum of 3 months. Clinical data were collected at baseline and after 6 months of treatment. The study analyzed the event-free survival at 6 months and all-cause death over 2 years. At baseline, the distribution of patients among the risk groups was as follows: 22 in the low-risk group, 35 in the intermediate-low-risk group, 91 in the intermediate-high-risk group, and 44 in the high-risk group. After 6 months of treatment, the oral sequential triple combination therapy resulted in reduced NT-proBNP levels (media from 1604 to 678 pg/mL), a decline in the percentage of WHO-FC III/IV (from 79.2% to 60.4%), an increased in the 6MWD (from 325 ± 147 to 378 ± 143 m) and a rise in the percentage of patients with three low-risk criteria (from 5.7% to 13.5%). Among the low-risk group, there was an improvement in the right heart remodeling, marked by a decrease in right atrium area and eccentricity index. The intermediate-low-risk group exhibited significant enhancements in WHO-FC and tricuspid annular plane systolic excursion. For those in the intermediate-high and high-risk groups, there were marked improvements in activity tolerance, as reflected by WHO-FC and 6MWD. The event-free survival rate at 6 months stood at 88%. Over the long-term follow-up, the survival rates at 1 and 2 years were 86.5% and 86.0%, respectively. In conclusion, the oral sequential triple combination therapy enhanced both exercise capacity and cardiac remodeling across PAH patients of different risk stratifications.

Bilayer t-J-J_{⊥} Model and Magnetically Mediated Pairing in the Pressurized Nickelate La_{3}Ni_{2}O_{7}.

The recently discovered nickelate superconductor La_{3}Ni_{2}O_{7} has a high transition temperature near 80 K under pressure, providing an additional avenue for exploring unconventional superconductivity. Here, with state-of-the-art tensor-network methods, we study a bilayer t-J-J_{⊥} model for La_{3}Ni_{2}O_{7} and find a robust s-wave superconductive (SC) order mediated by interlayer magnetic couplings. Large-scale density matrix renormalization group calculations find algebraic pairing correlations with Luttinger parameter K_{SC}≲1. Infinite projected entangled-pair state method obtains a nonzero SC order directly in the thermodynamic limit, and estimates a strong pairing strength Δ[over ¯]_{z}∼O(0.1). Tangent-space tensor renormalization group simulations elucidate the temperature evolution of SC pairing and further determine a high SC temperature T_{c}^{*}/J∼O(0.1). Because of the intriguing orbital selective behaviors and strong Hund's rule coupling in the compound, t-J-J_{⊥} model has strong interlayer spin exchange (while negligible interlayer hopping), which greatly enhances the SC pairing in the bilayer system. Such a magnetically mediated pairing has also been observed recently in the optical lattice of ultracold atoms. Our accurate and comprehensive tensor-network calculations reveal a robust SC order in the bilayer t-J-J_{⊥} model and shed light on the pairing mechanism of the high-T_{c} nickelate superconductor.

Effects of Bone Marrow Mesenchymal Stem Cell-Derived Exosomes in Central Nervous System Diseases.

Central nervous system (CNS) diseases are one of the diseases that threaten human health. The delivery of drugs targeting the CNS has always been a significant challenge; the blood-brain barrier (BBB) is the main obstacle that must be overcome. The rise of bone marrow mesenchymal stem cell (BMSC) therapy has brought hope for the treatment of CNS diseases. However, the problems of low homing rate, susceptibility differentiation into astrocytes, immune rejection, and formation of iatrogenic tumors of transplanted BMSCs limit their clinical application. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) have become a hot research topic in the treatment of CNS diseases in recent years because of their excellent histocompatibility, low immunogenicity, ease of crossing the BBB, and their ability to serve as natural carriers for treatment. This article reviews the mechanisms of BMSC-Exos in CNS diseases and provides direction for further research.

Giant magnetocaloric effect in spin supersolid candidate Na2BaCo(PO4)2.

Supersolid, an exotic quantum state of matter that consists of particles forming an incompressible solid structure while simultaneously showing superfluidity of zero viscosity1, is one of the long-standing pursuits in fundamental research2,3. Although the initial report of 4He supersolid turned out to be an artefact4, this intriguing quantum matter has inspired enthusiastic investigations into ultracold quantum gases5-8. Nevertheless, the realization of supersolidity in condensed matter remains elusive. Here we find evidence for a quantum magnetic analogue of supersolid-the spin supersolid-in the recently synthesized triangular-lattice antiferromagnet Na2BaCo(PO4)2 (ref. 9). Notably, a giant magnetocaloric effect related to the spin supersolidity is observed in the demagnetization cooling process, manifesting itself as two prominent valley-like regimes, with the lowest temperature attaining below 100 mK. Not only is there an experimentally determined series of critical fields but the demagnetization cooling profile also shows excellent agreement with the theoretical simulations with an easy-axis Heisenberg model. Neutron diffractions also successfully locate the proposed spin supersolid phases by revealing the coexistence of three-sublattice spin solid order and interlayer incommensurability indicative of the spin superfluidity. Thus, our results reveal a strong entropic effect of the spin supersolid phase in a frustrated quantum magnet and open up a viable and promising avenue for applications in sub-kelvin refrigeration, especially in the context of persistent concerns about helium shortages10,11.

Tumor-derived extracellular vesicles: how they mediate glioma immunosuppression.

Gliomas, the most common malignant brain tumor, present a grim prognosis despite available treatments such as surgical resection, temozolomide (TMZ) therapy, and radiation therapy. This is due to their aggressive growth, high level of immunosuppression, and the blood-brain barrier (BBB), which obstruct the effective exchange of therapeutic drugs. Gliomas can significantly affect differentiation and function of immune cells by releasing extracellular vesicles (EVs), resulting in a systemic immunosuppressive state and a highly immunosuppressive microenvironment. In the tumor immune microenvironment (TIME), the primary immune cells are regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs). In particular, glioma-associated TAMs are chiefly composed of monocyte-derived macrophages and brain-resident microglia. These cells partially exhibit characteristics of a pro-tumorigenic, anti-inflammatory M2-type. Glioma-derived EVs can hijack TAMs to differentiate into tumor-supporting phenotypes or directly affect the maturation of peripheral blood monocytes (PBMCs) and promote the activation of MDSCs. In addition, EVs impair the ability of dendritic cells (DCs) to process antigens, subsequently hindering the activation of lymphocytes. EVs also impact the proliferation, differentiation, and activation of lymphocytes. This is primarily evident in the overall reduction of CD4 + helper T cells and CD8 + T cells, coupled with a relative increase in Tregs, which possess immunosuppressive characteristics. This study investigates thoroughly how tumor-derived EVs impair the function of immune cells and enhance immunosuppression in gliomas, shedding light on their potential implications for immunotherapy strategies in glioma treatment.

Phonon vortices at heavy impurities in two-dimensional materials.

The advent of monochromated electron energy-loss spectroscopy has enabled atomic-resolution vibrational spectroscopy, which triggered interest in spatially localized or quasi-localized vibrational modes in materials. Here we report the discovery of phonon vortices at heavy impurities in two-dimensional materials. We use density-functional-theory calculations for two configurations of Si impurities in graphene, Si-C3 and Si-C4, to examine atom-projected phonon densities of states and display the atomic-displacement patterns for select modes that are dominated by impurity displacements. The vortices are driven by large displacements of the impurities, and reflect local symmetries. Similar vortices are found at phosphorus impurities in hexagonal boron nitride, suggesting that they may be a feature of heavy impurities in crystalline materials. Phonon vortices at defects are expected to play a role in thermal conductivity and other properties.

Research progress on mechanisms of ischemic stroke: Regulatory pathways involving Microglia.

Microglia, as the intrinsic immune cells in the brain, are activated following ischemic stroke. Activated microglia participate in the pathological processes after stroke through polarization, autophagy, phagocytosis, pyroptosis, ferroptosis, apoptosis, and necrosis, thereby influencing the injury and repair following stroke. It has been established that polarized M1 and M2 microglia exhibit pro-inflammatory and anti-inflammatory effects, respectively. Autophagy and phagocytosis in microglia following ischemia are dynamic processes, where moderate levels promote cell survival, while excessive responses may exacerbate neurofunctional deficits following stroke. Additionally, pyroptosis and ferroptosis in microglia after ischemic stroke contribute to the release of harmful cytokines, further aggravating the damage to brain tissue due to ischemia. This article discusses the different functional states of microglia in ischemic stroke research, highlighting current research trends and gaps, and provides insights and guidance for further study of ischemic stroke.

Polymeric Electrolytes for Solid-state Lithium Ion Batteries: Structure Design, Electrochemical Properties and Cell Performances.

Solid-state electrolytes are key to achieving high energy density, safety, and stability for lithium-ion batteries. In this Review, core indicators of solid polymer electrolytes are discussed in detail including ionic conductivity, interface compatibility, mechanical integrity, and cycling stability. Besides, we also summarize how above properties can be improved by design strategies of functional monomers, groups, and assembly of batteries. Structures and properties of polymers are investigated here to provide a basis for all-solid-state electrolyte design strategies of multi-component polymers. In addition, adjustment strategies of quasi-solid-state polymer electrolytes such as adding functional additives and carrying out structural design are also investigated, aiming at solving problems caused by simply adding liquids or small molecular plasticizer. We hope that fresh and established researchers can achieve a general perspective of solid polymer electrolytes via this Review and spur more extensive interests for exploration of high-performance lithium-ion batteries.

A versatile model with three-dimensional triangular lattice for unconventional transport and various topological effects.

The finite Berry curvature in topological materials can induce many subtle phenomena, such as the anomalous Hall effect (AHE), spin Hall effect (SHE), anomalous Nernst effect (ANE), non-linear Hall effect (NLHE) and bulk photovoltaic effects. To explore these novel physics as well as their connection and coupling, a precise and effective model should be developed. Here, we propose such a versatile model-a 3D triangular lattice with alternating hopping parameters, which can yield various topological phases, including kagome bands, triply degenerate fermions, double Weyl semimetals and so on. We reveal that this special lattice can present unconventional transport due to its unique topological surface states and the aforementioned topological phenomena, such as AHE, ANE, NLHE and the topological photocurrent effect. In addition, we also provide a number of material candidates that have been synthesized experimentally with this lattice, and discuss two materials, including a non-magnetic triangular system for SHE, NLHE and the shift current, and a ferromagnetic triangular lattice for AHE and ANE. Our work provides an excellent platform, including both the model and materials, for the study of Berry-curvature-related physics.

Novel Strategies for Angiogenesis in Tissue Injury: Therapeutic Effects of iPSCs-Derived Exosomes.

Regeneration after tissue injury is a dynamic and complex process, and angiogenesis is necessary for normal physiological activities and tissue repair. Induced pluripotent stem cells are a new approach in regenerative medicine, which provides good model for the study of difficult-to-obtain human tissues, patient-specific therapy, and tissue repair. As an innovative cell-free therapeutic strategy, the main advantages of the treatment of induced pluripotent stem cells (iPSCs)-derived exosomes are low in tumorigenicity and immunogenicity, which become an important pathway for tissue injury. This review focuses on the mechanism of the angiogenic effect of iPSCs-derived exosomes on wound repair in tissue injury and their potential therapeutic targets, with a view to providing a theoretical basis for the use of iPSCs-derived exosomes in clinical therapy.

Superconducting, Topological, and Transport Properties of Kagome Metals CsTi3Bi5 and RbTi3Bi5.

The recently discovered ATi3Bi5 (A=Cs, Rb) exhibit intriguing quantum phenomena including superconductivity, electronic nematicity, and abundant topological states. ATi3Bi5 present promising platforms for studying kagome superconductivity, band topology, and charge orders in parallel with AV3Sb5. In this work, we comprehensively analyze various properties of ATi3Bi5 covering superconductivity under pressure and doping, band topology under pressure, thermal conductivity, heat capacity, electrical resistance, and spin Hall conductivity (SHC) using first-principles calculations. Calculated superconducting transition temperature (Tc) of CsTi3Bi5 and RbTi3Bi5 at ambient pressure are about 1.85 and 1.92 K. When subject to pressure, Tc of CsTi3Bi5 exhibits a special valley and dome shape, which arises from quasi-two-dimensional compression to three-dimensional isotropic compression within the context of an overall decreasing trend. Furthermore, Tc of RbTi3Bi5 can be effectively enhanced up to 3.09 K by tuning the kagome van Hove singularities (VHSs) and flat band through doping. Pressures can also induce abundant topological surface states at the Fermi energy (EF) and tune VHSs across EF. Additionally, our transport calculations are in excellent agreement with recent experiments, confirming the absence of charge density wave. Notably, SHC of CsTi3Bi5 can reach up to 226ℏ ·(e· Ω ·cm)-1 at EF. Our work provides a timely and detailed analysis of the rich physical properties for ATi3Bi5, offering valuable insights for further experimental verifications and investigations in this field.

Symmetry dictionary on charge and spin nonlinear responses for all magnetic point groups with nontrivial topological nature.

Recently, charge or spin nonlinear transport with nontrivial topological properties in crystal materials has attracted much attention. In this paper, we perform a comprehensive symmetry analysis for all 122 magnetic point groups (MPGs) and provide a useful dictionary for charge and spin nonlinear transport from the Berry curvature dipole, Berry connection polarizability and Drude term with nontrivial topological nature. The results are obtained by conducting a full symmetry investigation of the matrix representations of six nonlinear response tensors. We further identify every MPG that can accommodate two or three of the nonlinear tensors. The present work gives a solid theoretical basis for an overall understanding of the second-order nonlinear responses in realistic materials.

Plaquette Singlet Transition, Magnetic Barocaloric Effect, and Spin Supersolidity in the Shastry-Sutherland Model.

Inspired by recent experimental measurements [Guo et al., Phys. Rev. Lett. 124, 206602 (2020PRLTAO0031-900710.1103/PhysRevLett.124.206602); Jiménez et al., Nature (London) 592, 370 (2021)NATUAS0028-083610.1038/s41586-021-03411-8] on frustrated quantum magnet SrCu_{2}(BO_{3})_{2} under combined pressure and magnetic fields, we study the related spin-1/2 Shastry-Sutherland model using state-of-the-art tensor network methods. By calculating thermodynamics, correlations, and susceptibilities, we find, in zero magnetic field, not only a line of first-order dimer-singlet to plaquette-singlet phase transition ending with a critical point, but also signatures of the ordered plaquette-singlet transition with its critical end point terminating on this first-order line. Moreover, we uncover prominent magnetic barocaloric responses, a novel type of quantum correlation induced cooling effect, in the strongly fluctuating supercritical regime. Under finite fields, we identify a quantum phase transition from the plaquette-singlet phase to the spin supersolid phase that breaks simultaneously lattice translational and spin rotational symmetries. The present findings on the Shastry-Sutherland model are accessible in current experiments and would shed new light on the critical and supercritical phenomena in the archetypal frustrated quantum magnet SrCu_{2}(BO_{3})_{2}.

Identification of the shared gene signatures between pulmonary fibrosis and pulmonary hypertension using bioinformatics analysis.

Pulmonary fibrosis (PF) and pulmonary hypertension (PH) have common pathophysiological features, such as the significant remodeling of pulmonary parenchyma and vascular wall. There is no effective specific drug in clinical treatment for these two diseases, resulting in a worse prognosis and higher mortality. This study aimed to screen the common key genes and immune characteristics of PF and PH by means of bioinformatics to find new common therapeutic targets. Expression profiles are downloaded from the Gene Expression Database. Weighted gene co-expression network analysis is used to identify the co-expression modules related to PF and PH. We used the ClueGO software to enrich and analyze the common genes in PF and PH and obtained the protein-protein interaction (PPI) network. Then, the differential genes were screened out in another cohort of PF and PH, and the shared genes were crossed. Finally, RT-PCR verification and immune infiltration analysis were performed on the intersection genes. In the result, the positive correlation module with the highest correlation between PF and PH was determined, and it was found that lymphocyte activation is a common feature of the pathophysiology of PF and PH. Eight common characteristic genes (ACTR2, COL5A2, COL6A3, CYSLTR1, IGF1, RSPO3, SCARNA17 and SEL1L) were gained. Immune infiltration showed that compared with the control group, resting CD4 memory T cells were upregulated in PF and PH. Combining the results of crossing characteristic genes in ImmPort database and RT-PCR, the important gene IGF1 was obtained. Knocking down IGF1 could significantly reduce the proliferation and apoptosis resistance in pulmonary microvascular endothelial cells, pulmonary smooth muscle cells, and fibroblasts induced by hypoxia, platelet-derived growth factor-BB (PDGF-BB), and transforming growth factor-ß1 (TGF-ß1), respectively. Our work identified the common biomarkers of PF and PH and provided a new candidate gene for the potential therapeutic targets of PF and PH in the future.

Possible intermediate quantum spin liquid phase in α-RuCl3 under high magnetic fields up to 100 T.

Pursuing the exotic quantum spin liquid (QSL) state in the Kitaev material α-RuCl3 has intrigued great research interest recently. A fascinating question is on the possible existence of a field-induced QSL phase in this compound. Here we perform high-field magnetization measurements of α-RuCl3 up to 102 T employing the non-destructive and destructive pulsed magnets. Under the out-of-plane field along the c* axis (i.e., perpendicular to the honeycomb plane), two quantum phase transitions are uncovered at respectively 35 T and about 83 T, between which lies an intermediate phase as the predicted QSL. This is in sharp contrast to the case with in-plane fields, where a single transition is found at around 7 T and the intermediate QSL phase is absent instead. By measuring the magnetization data with fields tilted from the c* axis up to 90° (i.e., in-plane direction), we obtain the field-angle phase diagram that contains the zigzag, paramagnetic, and QSL phases. Based on the K-J-Γ-[Formula: see text] model for α-RuCl3 with a large Kitaev term we perform density matrix renormalization group simulations and reproduce the quantum phase diagram in excellent agreement with experiments.

Observation of flat band, Dirac nodal lines and topological surface states in Kagome superconductor CsTi3Bi5.

Kagome lattices of various transition metals are versatile platforms for achieving anomalous Hall effects, unconventional charge-density wave orders and quantum spin liquid phenomena due to the strong correlations, spin-orbit coupling and/or magnetic interactions involved in such a lattice. Here, we use laser-based angle-resolved photoemission spectroscopy in combination with density functional theory calculations to investigate the electronic structure of the newly discovered kagome superconductor CsTi3Bi5, which is isostructural to the AV3Sb5 (A = K, Rb or Cs) kagome superconductor family and possesses a two-dimensional kagome network of titanium. We directly observe a striking flat band derived from the local destructive interference of Bloch wave functions within the kagome lattice. In agreement with calculations, we identify type-II and type-III Dirac nodal lines and their momentum distribution in CsTi3Bi5 from the measured electronic structures. In addition, around the Brillouin zone centre, [Formula: see text] nontrivial topological surface states are also observed due to band inversion mediated by strong spin-orbit coupling.