Distinctive Structural and Molecular Features of Myelinated Inhibitory Axons in Human Neocortex.

Numerous types of inhibitory neurons sculpt the performance of human neocortical circuits, with each type exhibiting a constellation of subcellular phenotypic features in support of its specialized functions. Axonal myelination has been absent among the characteristics used to distinguish inhibitory neuron types; in fact, very little is known about myelinated inhibitory axons in human neocortex. Here, using array tomography to analyze samples of neurosurgically excised human neocortex, we show that inhibitory myelinated axons originate predominantly from parvalbumin-containing interneurons. Compared to myelinated excitatory axons, they have higher neurofilament and lower microtubule content, shorter nodes of Ranvier, and more myelin basic protein (MBP) in their myelin sheath. Furthermore, these inhibitory axons have more mitochondria, likely to sustain the high energy demands of parvalbumin interneurons, as well as more 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP), a protein enriched in the myelin cytoplasmic channels that are thought to facilitate the delivery of nutrients from ensheathing oligodendrocytes. Our results demonstrate that myelinated axons of parvalbumin inhibitory interneurons exhibit distinctive features that may support the specialized functions of this neuron type in human neocortical circuits

Negative flat band magnetism in a spin-orbit coupled correlated kagome magnet

It has long been speculated that electronic flat band systems can be a fertile ground for hosting novel emergent phenomena including unconventional magnetism and superconductivity. Although flat bands are known to exist in a few systems such as heavy fermion materials and twisted bilayer graphene, their microscopic roles and underlying mechanisms in generating emergent behavior remain elusive. Here we use scanning tunneling microscopy to elucidate the atomically resolved electronic states and their magnetic response in the kagome magnet Co3Sn2S2. We observe a pronounced peak at the Fermi level, which is identified to arise from the kinetically frustrated kagome flat band. Increasing magnetic field up to +-8T, this state exhibits an anomalous magnetization-polarized Zeeman shift, dominated by an orbital moment in opposite to the field direction. Such negative magnetism can be understood as spin-orbit coupling induced quantum phase effects tied to non-trivial flat band systems. We image the flat band peak, resolve the associated negative magnetism, and provide its connection to the Berry curvature field, showing that Co3Sn2S2 is a rare example of kagome magnet where the low energy physics can be dominated by the spin-orbit coupled flat band. Our methodology of probing band-resolved ordering phenomena such as spin-orbit magnetism can also be applied in future experiments to elucidate other exotic phenomena including flat band superconductivity and anomalous quantum transport.Comment: Nature Physics onlin

CD274 (PD-L1) negatively regulates M1 macrophage polarization in ALI/ARDS

BackgroundAcute lung injury (ALI)/severe acute respiratory distress syndrome (ARDS) is a serious clinical syndrome characterized by a high mortality rate. The pathophysiological mechanisms underlying ALI/ARDS remain incompletely understood. Considering the crucial role of immune infiltration and macrophage polarization in the pathogenesis of ALI/ARDS, this study aims to identify key genes associated with both ALI/ARDS and M1 macrophage polarization, employing a combination of bioinformatics and experimental approaches. The findings could potentially reveal novel biomarkers for the diagnosis and management of ALI/ARDS.MethodsGene expression profiles relevant to ALI were retrieved from the GEO database to identify co-upregulated differentially expressed genes (DEGs). GO and KEGG analyses facilitated functional annotation and pathway elucidation. PPI networks were constructed to identify hub genes, and differences in immune cell infiltration were subsequently examined. The expression of hub genes in M1 versus M2 macrophages was evaluated using macrophage polarization datasets. The diagnostic utility of CD274 (PD-L1) for ARDS was assessed by receiver operating characteristic (ROC) analysis in a validation dataset. Experimental confirmation was conducted using two LPS-induced M1 macrophage models and an ALI mouse model. The role of CD274 (PD-L1) in M1 macrophage polarization and associated proinflammatory cytokine production was further investigated by siRNA-mediated silencing.ResultsA total of 99 co-upregulated DEGs were identified in two ALI-linked datasets. Enrichment analysis revealed that these DEGs were mainly involved in immune-inflammatory pathways. The following top 10 hub genes were identified from the PPI network: IL-6, IL-1β, CXCL10, CD274, CCL2, TLR2, CXCL1, CCL3, IFIT1, and IFIT3. Immune infiltration analysis revealed a significantly increased abundance of M1 and M2 macrophages in lung tissue from the ALI group compared to the control group. Subsequent analysis confirmed that CD274 (PD-L1), a key immunological checkpoint molecule, was highly expressed within M1 macrophages. ROC analysis validated CD274 (PD-L1) as a promising biomarker for the diagnosis of ARDS. Both in vitro and in vivo experiments supported the bioinformatics analysis and confirmed that the JAK-STAT3 pathway promotes CD274 (PD-L1) expression on M1 macrophages. Importantly, knockdown of CD274 (PD-L1) expression potentiated M1 macrophage polarization and enhanced proinflammatory cytokines production.ConclusionThis study demonstrates a significant correlation between CD274 (PD-L1) and M1 macrophages in ALI/ARDS. CD274 (PD-L1) functions as a negative regulator of M1 polarization and the secretion of proinflammatory cytokines in macrophages. These findings suggest potential new targets for the diagnosis and treatment of ALI/ARDS

Nonlinear Bloch wave dynamics in photonic Aharonov–Bohm cages

We study the properties of nonlinear Bloch waves in a diamond chain waveguide lattice in the presence of a synthetic magnetic flux. In the linear limit, the lattice exhibits a completely flat (wavevector k-independent) band structure, resulting in perfect wave localization, known as Aharonov-Bohm caging. We find that in the presence of nonlinearity, the Bloch waves become sensitive to k, exhibiting bifurcations and instabilities. Performing numerical beam propagation simulations using the tight-binding model, we show how the instabilities can result in either the spontaneous or controlled formation of localized modes, which are immobile and remain pinned in place due to the synthetic magnetic flux. © 2021 Author(s

Minimising efficiency roll-off in high-brightness perovskite light-emitting diodes.

Efficiency roll-off is a major issue for most types of light-emitting diodes (LEDs), and its origins remain controversial. Here we present investigations of the efficiency roll-off in perovskite LEDs based on two-dimensional layered perovskites. By simultaneously measuring electroluminescence and photoluminescence on a working device, supported by transient photoluminescence decay measurements, we conclude that the efficiency roll-off in perovskite LEDs is mainly due to luminescence quenching which is likely caused by non-radiative Auger recombination. This detrimental effect can be suppressed by increasing the width of quantum wells, which can be easily realized in the layered perovskites by tuning the ratio of large and small organic cations in the precursor solution. This approach leads to the realization of a perovskite LED with a record external quantum efficiency of 12.7%, and the efficiency remains to be high, at approximately 10%, under a high current density of 500 mA cm-2

Hepcidin is upregulated and is a potential therapeutic target associated with immunity in glioma

BackgroundGlioma is the most common primary malignant brain tumor with high mortality and poor prognosis. Hepcidin is a fascinating iron metabolism regulator. However, the prognostic value of hepcidin HAMP in gliomas and its correlation with immune cell infiltration remain unclear. Here, we comprehensively elucidate the prognostic value and potential role of hepcidin in gliomas.MethodsHepcidin gene expression and clinical characteristics in glioma were analyzed using the CGGA, TCGA, Rembrandt and Gravendeel glioma databases. A survival analysis was conducted using Kaplan–Meier and Cox regression analyses. A gene set enrichment analysis (GSEA) was conducted to select the pathways significantly enriched for hepcidin associations. The correlations between hepcidin and immune cell infiltration and immunotherapy were analyzed using network platforms such as CIBERSORT and TIMER.ResultsIn glioma tissues, the expression of hepcidin was significantly increased. High hepcidin expression is related to grade, age, PRS type, IDH mutation, chemotherapy status and 1p19q codeletion status, which significantly indicates the poor prognosis of glioma patients. Hepcidin can be used as an independent prognostic factor for glioma through the multivariate COX regression analysis. The results of Gene Ontology (GO), Kyoto Encyclopedia of Gene and Genome (KEGG) and gene set enrichment analysis (GSEA) indicated that hepcidin was involved in the immune response. In addition, hepcidin expression was positively correlated with the degree of immune cell infiltration, the expression of various immune cell markers and the efficacy of immunotherapy.ConclusionOur results indicate that hepcidin can be used as a candidate biomarker to judge the prognosis and immune cell invasion of gliomas