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.

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.

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.

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.

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.

Magnetocaloric effect of topological excitations in Kitaev magnets.

Traditional magnetic sub-Kelvin cooling relies on the nearly free local moments in hydrate paramagnetic salts, whose utility is hampered by the dilute magnetic ions and low thermal conductivity. Here we propose to use instead fractional excitations inherent to quantum spin liquids (QSLs) as an alternative, which are sensitive to external fields and can induce a very distinctive magnetocaloric effect. With state-of-the-art tensor-network approach, we compute low-temperature properties of Kitaev honeycomb model. For the ferromagnetic case, strong demagnetization cooling effect is observed due to the nearly free Z2 vortices via spin fractionalization, described by a paramagnetic equation of state with a renormalized Curie constant. For the antiferromagnetic Kitaev case, we uncover an intermediate-field gapless QSL phase with very large spin entropy, possibly due to the emergence of spinon Fermi surface and gauge field. Potential realization of topological excitation magnetocalorics in Kitaev materials is also discussed, which may offer a promising pathway to circumvent existing limitations in the paramagnetic hydrates.

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.

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.

Pharmacologic Inhibition of Ferroptosis Attenuates Experimental Abdominal Aortic Aneurysm Formation.

The pathogenesis of abdominal aortic aneurysm (AAA) formation involves vascular inflammation, thrombosis formation and programmed cell death leading to aortic remodeling. Recent studies have suggested that ferroptosis, an excessive iron-mediated cell death, can regulate cardiovascular diseases, including AAAs. However, the role of ferroptosis in immune cells, like macrophages, and ferroptosis-related genes in AAA formation remains to be deciphered. Single cell-RNA sequencing of human aortic tissue from AAA patients demonstrates significant differences in ferroptosis-related genes compared to control aortic tissue. Using two established murine models of AAA and aortic rupture in C57BL/6 (WT) mice, we observed that treatment with liproxstatin-1, a specific ferroptosis inhibitor, significantly attenuated aortic diameter, pro-inflammatory cytokine production, immune cell infiltration (neutrophils and macrophages), increased smooth muscle cell α-actin expression and elastic fiber disruption compared to mice treated with inactivated elastase in both pre-treatment and treatment after a small AAA had already formed. Lipidomic analysis using mass spectrometry shows a significant increase in ceramides and a decrease in intact lipid species levels in murine tissue compared to controls in the chronic AAA model on day 28. Mechanistically, in vitro studies demonstrate that liproxstatin-1 treatment of macrophages mitigated the crosstalk with aortic smooth muscle cells (SMCs) by downregulating MMP2 secretion. Taken together, this study demonstrates that pharmacological inhibition by liproxstatin-1 mitigates macrophage-dependent ferroptosis contributing to inhibition of aortic inflammation and remodeling during AAA formation.

Gut microbiota microbial metabolites in diabetic nephropathy patients: far to go.

Diabetic nephropathy (DN) is one of the main complications of diabetes and a major cause of end-stage renal disease, which has a severe impact on the quality of life of patients. Strict control of blood sugar and blood pressure, including the use of renin-angiotensin-aldosterone system inhibitors, can delay the progression of diabetic nephropathy but cannot prevent it from eventually developing into end-stage renal disease. In recent years, many studies have shown a close relationship between gut microbiota imbalance and the occurrence and development of DN. This review discusses the latest research findings on the correlation between gut microbiota and microbial metabolites in DN, including the manifestations of the gut microbiota and microbial metabolites in DN patients, the application of the gut microbiota and microbial metabolites in the diagnosis of DN, their role in disease progression, and so on, to elucidate the role of the gut microbiota and microbial metabolites in the occurrence and prevention of DN and provide a theoretical basis and methods for clinical diagnosis and treatment.

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.

Pulmonary vascular resistance predicts the mortality in patients with bronchiectasis-associated pulmonary hypertension.

OBJECTIVE: Pulmonary hypertension is a severe complication of bronchiectasis, characterized by elevated pulmonary vascular resistance (PVR) and subsequent right heart failure. The association between PVR and mortality in bronchiectasis-associated pulmonary hypertension has not been investigated previously. METHODS: In the present study, a retrospective analysis was conducted on 139 consecutive patients diagnosed with bronchiectasis-associated pulmonary hypertension based on right heart catheterization, enrolled between January 2010 and June 2023. Baseline clinical characteristics and hemodynamic assessment were analyzed. The survival time for each patient was calculated in months from the date of diagnosis until the date of death or, if the patient was still alive, until their last visit. RESULTS: Patients with bronchiectasis-associated pulmonary hypertension exhibited estimated survival rates of 89.5, 70, and 52.9 at 1-year, 3-year, and 5-year intervals respectively, with a median survival time of 67 months. Multivariable Cox regression analysis revealed that increased age [(adjusted hazard ratio per year 1.042, 95% confidence interval (CI) 1.008-1.076, P = 0.015] and elevated PVR (adjusted HR per 1 Wood Units 1.115, 95% CI 1.015-1.224, P = 0.023) were associated with an increased risk of all-cause mortality. In contrast, higher BMI was associated with a decreased risk of all-cause death (adjusted hazard ratio per 1 kg/m2 0.915, 95% CI 0.856-0.979, P = 0.009). Receiver-operating characteristic analyses identified a cutoff value for PVR at 4 Wood Units as predictive for all-cause death within 3 years [area under the curve (AUC) = 0.624; specificity= 87.5%; sensitivity= 35.8%; P < 0.05]. Patients with a PVR greater than 4 Wood Units had a significantly higher risk of all-cause death compared with those with 4 Wood Units or less (adjusted hazard ratio 2.392; 95% CI 1.316-4.349; P = 0.019). Notably, there were no significant differences in age, sex, BMI, WHO functional class, 6-min walk distance, and NT-proBNP levels at baseline between patients categorized as having 4 Wood Units or less or greater than 4 Wood Units for PVR. CONCLUSION: Based on these data, PVR could serve as a discriminative marker for distinguishing between nonsevere pulmonary hypertension (PVR ≤ 4 Wood Units) and severe pulmonary hypertension (PVR > 4 Wood Units). The utilization of a PVR cutoff value of 4.0 Wood Units provides enhanced prognostic capabilities for predicting mortality.

Serum ASGR2 level: an efficacy biomarker for balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension.

Background: This study aimed to employ plasma proteomics to investigate the molecular changes, pathway alterations, and potential novel biochemical markers associated with balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: Pre- and post-BPA plasma samples from five CTEPH patients in the PRACTICE study were analyzed to identify differentially expressed proteins. Proteomic and bioinformatics analyses were conducted, and the identified proteins were further validated using ELISA assays in a separate cohort of the same study. Correlation and multivariate regression analyses were performed to investigate the associations between these differentially expressed proteins and clinical parameters. Results: Significantly higher serum levels of asialoglycoprotein receptor 2 (ASGR2) were detected in 5 CTEPH patients compared to those in healthy individuals but decreased significantly after successful BPA procedures. The decrease in serum levels of ASGR2 after the completion of BPA procedures was further validated in a separate cohort of 48 patients with CTEPH [0.70 (0.51, 1.11) ng/mL vs. 0.38 (0.27, 0.59) ng/mL, P < 0.001]. Significant associations were found between the pre-BPA ASGR2 level and clinical parameters, including neutrophil percentage (R = 0.285, P < 0.05), platelet (PLT) count (R = 0.386, P < 0.05), and high-density lipoprotein cholesterol (HDL-C) before BPA (R = -0.285, P < 0.05). Significant associations were detected between post-BPA serum ASGR2 levels and lymphocyte percentage (LYM%) (R = 0.306, P < 0.05), neutrophil-to-lymphocyte ratio (R = -0.294, P < 0.05), and pulmonary vascular resistance after BPA (R = -0.35, P < 0.05). Multivariate stepwise regression analysis revealed that pre-BPA ASGR2 levels were associated with HDL-C and PLT count (both P < 0.001), while post-BPA ASGR2 levels were associated with LYM% (P < 0.05). Conclusion: Serum levels of ASGR2 may be a biomarker for the effectiveness of BPA treatment in CTEPH patients. The pre-BPA serum level of ASGR2 in CTEPH patients was associated with HDL-C and the PLT count. The post-BPA serum level of ASGR2 was correlated with the LYM%, which may reflect aspects of immune and inflammatory status.