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.

Single-atom vibrational spectroscopy with chemical-bonding sensitivity.

Correlation of lattice vibrational properties with local atomic configurations in materials is essential for elucidating functionalities that involve phonon transport in solids. Recent developments in vibrational spectroscopy in a scanning transmission electron microscope have enabled direct measurements of local phonon modes at defects and interfaces by combining high spatial and energy resolution. However, pushing the ultimate limit of vibrational spectroscopy in a scanning transmission electron microscope to reveal the impact of chemical bonding on local phonon modes requires extreme sensitivity of the experiment at the chemical-bond level. Here we demonstrate that, with improved instrument stability and sensitivity, the specific vibrational signals of the same substitutional impurity and the neighbouring carbon atoms in monolayer graphene with different chemical-bonding configurations are clearly resolved, complementary with density functional theory calculations. The present work opens the door to the direct observation of local phonon modes with chemical-bonding sensitivity, and provides more insights into the defect-induced physics in graphene.

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.

Targeting p53 for neuroinflammation: New therapeutic strategies in ischemic stroke.

Ischemic stroke (IS) is characterized by high incidence, high recurrence, and high mortality and places a heavy burden on society and families. The pathological mechanisms of IS are complex, among which secondary neurological impairment mediated by neuroinflammation is considered to be the main factor in cerebral ischemic injury. At present, there is still a lack of specific therapies to treat neuroinflammation. The tumor suppressor protein p53 has long been regarded as a key substance in the regulation of the cell cycle and apoptosis in the past. Recently, studies have found that p53 also plays an important role in neuroinflammatory diseases, such as IS. Therefore, p53 may be a crucial target for the regulation of the neuroinflammatory response. Here, we provide a comprehensive review of the potential of targeting p53 in the treatment of neuroinflammation after IS. We describe the function of p53, the major immune cells involved in neuroinflammation, and the role of p53 in inflammatory responses mediated by these cells. Finally, we summarize the therapeutic strategies of targeting p53 in regulating the neuroinflammatory response after IS to provide new directions and ideas for the treatment of ischemic brain injury.

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}.

Resolution of inflammation via RvD1/FPR2 signaling mitigates Nox2 activation and ferroptosis of macrophages in experimental abdominal aortic aneurysms.

Abdominal aortic aneurysm (AAA) formation is characterized by inflammation, leukocyte infiltration, and vascular remodeling. Resolvin D1 (RvD1) is derived from ω-3 polyunsaturated fatty acids and is involved in the resolution phase of chronic inflammatory diseases. The aim of this study was to decipher the protective role of RvD1 via formyl peptide receptor 2 (FPR2) receptor signaling in attenuating abdominal aortic aneurysms (AAA). The elastase-treatment model of AAA in C57BL/6 (WT) mice and human AAA tissue was used to confirm our hypotheses. Elastase-treated FPR2-/- mice had a significant increase in aortic diameter, proinflammatory cytokine production, immune cell infiltration (macrophages and neutrophils), elastic fiber disruption, and decrease in smooth muscle cell α-actin expression compared to elastase-treated WT mice. RvD1 treatment attenuated AAA formation, aortic inflammation, and vascular remodeling in WT mice, but not in FPR2-/- mice. Importantly, human AAA tissue demonstrated significantly decreased FPR2 mRNA expression compared to non-aneurysm human aortas. Mechanistically, RvD1/FPR2 signaling mitigated p47phox phosphorylation and prevented hallmarks of ferroptosis, such as lipid peroxidation and Nrf2 translocation, thereby attenuating HMGB1 secretion. Collectively, this study demonstrates RvD1-mediated immunomodulation of FPR2 signaling on macrophages to mitigate ferroptosis and HMGB1 release, leading to resolution of aortic inflammation and remodeling during AAA pathogenesis.

Mechanism of ligusticum cycloprolactam against neuroinflammation based on network pharmacology and experimental verification.

Ligustilide, a natural phthalide mainly derived from chuanxiong rhizomes and Angelica Sinensis roots, possesses anti-inflammatory activity, particularly in the context of the nervous system. However, its application is limited because of its unstable chemical properties. To overcome this limitation, ligusticum cycloprolactam (LIGc) was synthesized through structural modification of ligustilide. In this study, we combined network pharmacological methods with experimental verification to investigate the anti-neuroinflammatory effects and mechanisms of ligustilide and LIGc. Based on our network pharmacology analysis, we identified four key targets of ligustilide involved in exerting an anti-inflammatory effect, with the nuclear factor (NF)-κB signal pathway suggested as the main signalling pathway. To verify these results, we examined the expression of inflammatory cytokines and inflammation-related proteins, analysed the phosphorylation level of NF-κB, inhibitor of κBα (IκBα) and inhibitor of κB kinase α and ß (IKKα+ß), and evaluated the effect of BV2 cell-conditioned medium on HT22 cells in vitro. Our results, demonstrate for the first time that LIGc can downregulate the activation of the NF-κB signal pathway in BV2 cells induced by lipopolysaccharide, suppress the production of inflammatory cytokines and reduce nerve injury in HT22 cells mediated by BV2 cells. These findings suggest that LIGc inhibits the neuroinflammatory response mediated by BV2 cells, providing strong scientific support for the development of anti-inflammatory drugs based on natural ligustilide or its derivatives. However, there are some limitations to our current study. In the future, further experiments using in vivo models may provide additional evidence to support our findings.

Exosome-derived miR-142-5p from liver stem cells improves the progression of liver fibrosis by regulating macrophage polarization through CTSB.

BACKGROUND: This study aims to explore the effect of liver stem cells (LSCs)-derived exosomes and the miR-142a-5p carried by them on the process of fibrosis by regulating macrophages polarization. METHODS: In this study, CCL4 was used to establish liver fibrosis model. The morphology and purity of exosomes (EVs) were verified by transmission electron microscopy, western blotting (WB) and nanoparticle tracing analysis (NTA). Real-time quantitative PCR (qRT-PCR), WB and enzyme-linked immunoadsorption (ELISA) were used to detect liver fibrosis markers, macrophage polarization markers and liver injury markers. Histopathological assays were used to verify the liver injury morphology in different groups. The cell co-culture model and liver fibrosis model were constructed to verify the expression of miR-142a-5p and ctsb. RESULTS: Immunofluorescence of LSCs markers CK-18, epithelial cell adhesion molecule (EpCam), and AFP showed that these markers were up-regulated in LSCs. In addition, we evaluated the ability of LSCs to excrete EVs by labeling LSCs-EVs with PKH67. We found that CCL4 and EVs were simultaneously treated at 50 and 100 µg doses, and both doses of EVs could reduce the degree of liver fibrosis in mice. We tested markers of M1 or M2 macrophage polarization and found that EVs reduced M1 marker expression and promoted M2 marker expression. Further, ELISA was used to detect the secreted factors related to M1 and M2 in tissue lysates, which also verified the above views. Further analysis showed that the expression of miR-142a-5p increased significantly with the increase of EVs treatment concentration and time. Further, in vitro and in vivo LSCs-EVs regulate macrophage polarization through miR-142a-5p/ctsb pathway and affect the process of liver fibrosis. CONCLUSION: Our data suggest that EVs-derived miR-142-5p from LSCs improves the progression of liver fibrosis by regulating macrophage polarization through ctsb.

Analysis of Risk Factors Related to the Efficacy of Foramen Ovale Closure as a Therapy for Migraine.

This study aimed to monitor the incidence of migraine non-remission after percutaneous patent foramen ovale (PFO) closure and to discuss relevant risk factors. Recently, evidence of a relationship between the presence of PFO and migraines has been found, and PFO closure has been pointed out as a possible treatment for migraineurs.A retrospective analysis was conducted, which involved 139 patients diagnosed with PFO and associated migraine who underwent percutaneous PFO closure in The First Affiliated Hospital of Zhengzhou University from October 2019 to April 2021. All the considered patients were evaluated using the Headache Impact Test (HIT-6™) and classified with a score higher than 55 points before closure. The HIT-6™ score was re-evaluated 1-6 months after the intervention. HIT-6™ ≤ 55 was defined as headache remission (n = 93) and > 55 as headache non-remission (n = 46). A logistic regression model was developed to identify the risk factors of headache non-remission after PFO closure.The incidence of headache non-remission after PFO closure was 33.09%. Statistically significant differences were observed between the two groups as regards age and serum phosphorus level (P < 0.05). History of smoking, atrial fibrillation, absolute lymphocyte count, platelet-to-lymphocyte ratio, and interventricular septal thickness were identified as independent risk factors for headache non-remission following PFO closure, which were statistically significant (P < 0.05).

Exposure to multiple metals in adults and diabetes mellitus: a cross-sectional analysis.

Diabetes mellitus (DM) is the most widely recognized metabolic illness with expanding morbidity among ongoing years. Its high incapacity rate and death rate badly affect individuals' quality of life. Increasing proofs backed the relationship between metal exposures with the risk of DM, but the methodological boundedness cannot clarify the complexity of the internal relationship of metal mixtures. We fitted the logistic regression model, weighted quantile sum regression model, and Bayesian kernel machine regression model to assess the relationship between the metal exposures with DM in adults who participated in the National Health and Nutrition Examination Survey 2013-2016. The metals (lead, cadmium, and copper) levels were significantly higher among diabetic compared to the healthy controls. In the logistic regression model established for each single metal, lead and manganese were associated with DM in both unadjusted and mutually adjusted models (highest vs. lowest concentration quartile). When considering all metal as a mixed exposure, we found a generally positive correlation between metal mixtures with DM (binary outcome) and glycohemoglobin (HbA1c) levels (continuous outcome). Exposure to metal mixtures was associated with an increased risk of DM and elevated levels of HbA1c.

Emergent Kagome Electrides.

In a two-dimensional (2D) Kagome lattice, the ideal Kagome bands including Dirac cones, van Hove singularities, and a flat band are highly expected, because they can provide a promising platform to investigate novel physical phenomena. However, in the reported Kagome materials, the complex 3D and multiorder electron hoppings result in the disappearance of the ideal Kagome bands in these systems. Here, we propose an alternative way to achieve the ideal Kagome bands in non-Kagome materials by confining excess electrons in the system to the crystal interstitial sites to form a 2D Kagome lattice, coined as a Kagome electride. Then, we predict two novel stable 2D Kagome electrides in hexagonal materials Li5Si and Li5Sn, whose band structures are similar to the ideal Kagome bands, including topological Dirac cones with beautiful Fermi arcs in their surface states, van Hove singularities, and a flat band. In addition, Li5Si is revealed to be a low-temperature superconductor at ambient pressure, and its superconducting transition temperature Tc can be increased from 1.1 K at 0 GPa to 7.2 K at 100 GPa. The high Tc is unveiled to be the consequence of strong electron-phonon coupling originated from the sp-hybridized phonon-coupled bands and phonon softening caused by strong Fermi nesting. Due to the strong Fermi nesting, the charge density wave phase transition occurs at 110 GPa with the lattice reconstructed from hexagonal to orthorhombic, accompanied with the increase of Tc to 10.5 K. Our findings pave an alternative way to fabricate more real materials with Kagome bands in electrides.

Maresin 1 activates LGR6 signaling to inhibit smooth muscle cell activation and attenuate murine abdominal aortic aneurysm formation.

The specialized pro-resolving lipid mediator maresin 1 (MaR1) is involved in the resolution phase of tissue inflammation. It was hypothesized that exogenous administration of MaR1 would attenuate abdominal aortic aneurysm (AAA) growth in a cytokine-dependent manner via LGR6 receptor signaling and macrophage-dependent efferocytosis of smooth muscle cells (SMCs). AAAs were induced in C57BL/6 wild-type (WT) mice and smooth muscle cell specific TGF-ß2 receptor knockout (SMC-TGFßr2-/- ) mice using a topical elastase AAA model. MaR1 treatment significantly attenuated AAA growth as well as increased aortic SMC α-actin and TGF-ß2 expressions in WT mice, but not SMC-TGFßr2-/- mice, compared to vehicle-treated mice. In vivo inhibition of LGR6 receptors obliterated MaR1-dependent protection in AAA formation and SMC α-actin expression. Furthermore, MaR1 upregulated macrophage-dependent efferocytosis of apoptotic SMCs in murine aortic tissue during AAA formation. In vitro studies demonstrate that MaR1-LGR6 interaction upregulates TGF-ß2 expression and decreases MMP2 activity during crosstalk of macrophage-apoptotic SMCs. In summary, these results demonstrate that MaR1 activates LGR6 receptors to upregulate macrophage-dependent efferocytosis, increases TGF-ß expression, preserves aortic wall remodeling and attenuate AAA formation. Therefore, this study demonstrates the potential of MaR1-LGR6-mediated mitigation of vascular remodeling through increased efferocytosis of apoptotic SMCs via TGF-ß2 to attenuate AAA formation.

Molecular Mechanism of the Protective Effects of M2 Microglia on Neurons: A Review Focused on Exosomes and Secretory Proteins.

Microglia, as innate immune cells in the brain, closely monitor changes in the internal environment and participate in the maintenance of homeostasis in the central nervous system (CNS). Microglia can be polarized to the M1 or M2 phenotype in response to various stimuli in vivo or in vitro, affecting the functions of peripheral neurons. M2 microglia have attracted increasing attention in recent years owing to their beneficial effects on various diseases and injuries of the CNS, such as traumatic brain injury, stroke, Alzheimer's disease and multiple sclerosis. They exert neuroprotective effects by various mechanisms, e.g., suppressing inflammation, promoting the degradation of misfolded and aggregated proteins, promoting neurite growth, enhancing neurogenesis, inhibiting autophagy and apoptosis, promoting myelination, maintaining blood-brain barrier integrity, and enhancing phagocytic activity.This review summarizes the molecular mechanisms by which M2 microglia exert protective effects on neurons and provides a reference for the selection of therapeutic targets for CNS diseases.

Peak oxygen uptake is a strong prognostic predictor for pulmonary hypertension due to left heart disease.

BACKGROUND: Pulmonary hypertension in left heart disease (PH-LHD), which includes combined post- and precapillary PH (Cpc-PH) and isolated postcapillary PH (Ipc-PH), differs significantly in prognosis. We aimed to assess whether cardiopulmonary exercise testing (CPET) predicts the long-term survival of patients with PH-LHD. METHODS: A single-center observational cohort enrolled 89 patients with PH-LHD who had undergone right heart catherization and CPET (mean pulmonary arterial pressure > 20 mm Hg and pulmonary artery wedge pressure ≥ 15 mm Hg) between 2013 and 2021. A receiver operating characteristic curve was plotted to determine the cutoff value of all-cause death. Survival was estimated using the Kaplan-Meier method and analyzed using the log-rank test. The Cox proportional hazards model was performed to determine the association between CPET and all-cause death. RESULTS: Seventeen patients died within a mean of 2.2 ± 1.3 years. Compared with survivors, nonsurvivors displayed a significantly worse 6-min walk distance, workload, exercise time and peak oxygen consumption (VO2)/kg with a trend of a lower oxygen uptake efficiency slope (OUES) adjusted by Bonferroni's correction. Multivariate Cox regression revealed that the peak VO2/kg was significantly associated with all-cause death after adjusting for Cpc-PH/Ipc-PH. Compared with Cpc-PH patients with a peak VO2/kg ≥ 10.7 ml kg-1 min-1, Ipc-PH patients with a peak VO2/kg < 10.7 ml kg-1 min-1 had a worse survival (P < 0.001). CONCLUSIONS: The peak VO2/kg is independently associated with all-cause death in patients with PH-LHD. The peak VO2/kg can also be analyzed together with Cpc-PH/Ipc-PH to better indicate the prognosis of patients with PH-LHD.

The effect of A2E on lysosome membrane permeability during blue light-induced human RPEs apoptosis.

BACKGROUND: To investigate the effect of N-retinyl-N-retinylidene ethanolamine (A2E) on lysosome membrane permeability (LMP) during blue light-induced human retinal pigment epithelium cells (RPEs) apoptosis. METHODS: By building an A2E and blue light irradiation inducing RPEs damage model, the CCK-8 assay was used to detect RPEs viability loaded with different concentrations of A2E after different culturing time to determine the optimum A2E loading concentration. And the RPEs fluorescence intensity changes were observed by fluorescence microscopy loaded with different concentration of A2E. The RPEs were divided into four groups randomly: control group, A2E-loaded group, blue light irradiation group, and A2E-loaded + blue light irradiation group. Annexin V-FITC/PI and TUNEL/DAPI methods were used to detect RPEs apoptotic rate. Laser scanning confocal microscopy (LSCM) was used to observe RPEs LMP changes stained by acridine orange (AO) method. RESULTS: The CCK-8 result showed a downward trend in cells viability of RPEs loaded with increasing concentration of A2E and extending culturing time. The optimum A2E loading concentration was determined at 25 µmol/L. With increasing A2E loading concentrations, the intensity of fluorescence in RPEs decreased gradually. The RPEs apoptotic rate in blue light irradiation + A2E-loaded group was significantly higher than those in other three groups detected by Annexin V-FITC/PI method, which was similar to TUNEL/DAPI's result. After AO staining, cytoplasmic and nucleolar RNAs emits green fluorescence; lysosomes emit red fluorescence. Through the interference of A2E and blue light on RPEs, red fluorescent leakage from the lysosomes (means LMP increasing) can be observed. The mean red fluorescence intensity was chosen as the statistics indicator to estimate LMP change in RPEs cultured in vitro. Compared with the control group, the red fluorescence intensity decreased in A2E-loaded group, blue light irradiation group, and blue light irradiation + A2E-loaded group. Meanwhile, the mean red fluorescence intensity in blue light irradiation + A2E-loaded group was the lowest. CONCLUSIONS: Both A2E-loaded and blue light irradiation could induce human RPEs apoptosis, and the two factors had a synergistic effect. In addition, both A2E and blue light can lead to LMP increasing, which indicated LMP change might be the upstream part in inducing mitochondrion-dependent apoptotic pathway. These data provided evidence that A2E as the most important auto-fluorescence substance in lipofuscin is an initiator of blue light-mediated damage of RPEs and participate in pathogenesis of retinal degenerative diseases in humans.

Multimodal imaging of the course of retinal changes in acute posterior multifocal placoid pigment epitheliopathy with bilateral retinal detachment: a case report.

BACKGROUND: To report a rare case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) with a combination of serous retinal detachment, papilledema, and retinal vasculitis. CASE PRESENTATION: A 19-year-old male complained of floaters in both eyes with decreased vision for 4 days. The best corrected visual acuity of the right eye and the left eye were 1.1 and 0.9 (logMAR), respectively. In both eyes, inflammatory cells can be seen suspended within the vitreous, multiple yellow/white lesions can be seen near the macula, and retinal neuroepithelial detachment. Swelling of the optic disc with blurring of the disc margins, in the left eye. Optical coherence tomography (OCT): showed retinal detachment in both eyes. The patient received oral prednisone treatment. 1 week later, OCT showed absorption of subretinal fluid in the macula of both eyes his binocular vision improved to 0.1 (logMAR). During the subsequent 28-month follow-up, fundus fluorescein angiography and OCT revealed extensive and progressive pigment epithelial atrophy in both eyes, and abnormal retinal vascular perfusion in the right eye due to persistent retinal vasculitis. Although the patient's binocular visual acuity remained at 0.1 (logMAR). CONCLUSIONS: In the present case of APMPPE with a combination of serous retinal detachment, papilledema, and retinal vasculitis, through the multimodal imaging, further confirming that the lesions were located in the choroid, while the pigment epithelial lesions were secondary changes.

Waterproof molecular monolayers stabilize 2D materials.

Two-dimensional van der Waals materials have rich and unique functional properties, but many are susceptible to corrosion under ambient conditions. Here we show that linear alkylamines n-C m H2m+1NH2, with m = 4 through 11, are highly effective in protecting the optoelectronic properties of these materials, such as black phosphorus (BP) and transition-metal dichalcogenides (TMDs: WS2, 1T'-MoTe2, WTe2, WSe2, TaS2, and NbSe2). As a representative example, n-hexylamine (m = 6) can be applied in the form of thin molecular monolayers on BP flakes with less than 2-nm thickness and can prolong BP's lifetime from a few hours to several weeks and even months in ambient environments. Characterizations combined with our theoretical analysis show that the thin monolayers selectively sift out water molecules, forming a drying layer to achieve the passivation of the protected 2D materials. The monolayer coating is also stable in air, H2 annealing, and organic solvents, but can be removed by certain organic acids.

Pharmacologic inhibition of transient receptor channel vanilloid 4 attenuates abdominal aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) formation is characterized by inflammation, leukocyte infiltration, and vascular remodeling. This study investigates the role of TRPV4 channels, which are transmembrane calcium channels that can regulate vascular tone, in modulating AAA formation. The elastase-treatment model of AAA in C57BL6 (WT) mice and Angiotensin II treatment model in ApoE-/- mice were used to confirm our hypotheses. The administration of a specific TRPV4 antagonist, GSK2193874, in elastase-treated WT mice and in AngII-treated ApoE-/- mice caused a significant attenuation of aortic diameter, decrease in pro-inflammatory cytokines (IL-1ß, IL-6, IL-17, MCP-1, MIP-1α, MIP-2, RANTES, and TNF-α), inflammatory cell infiltration (CD3 + T cells, macrophages, and neutrophils), elastic fiber disruption, and an increase in smooth muscle cell α-actin expression compared to untreated mice. Similarly, elastase-treated TRPV4-/- mice had a significant decrease in AAA formation, aortic inflammation, and vascular remodeling compared to elastase-treated WT mice on Day 14. In vitro studies demonstrated that the inhibition of TRPV4 channels mitigates aortic smooth muscle cell-dependent inflammatory cytokine production as well as decreases neutrophil transmigration through aortic endothelial cells. Therefore, our results suggest that TRPV4 antagonism can attenuate aortic inflammation and remodeling via decreased smooth muscle cell activation and neutrophil transendothelial migration during AAA formation.