Active thermal metasurfaces for remote heating/cooling by mimicking negative thermal conductivity

Remote temperature control can be obtained by a long-focus thermal lens that can focus heat fluxes into a spot far away from the back surface of the lens and create a virtual thermal source/sink in the background material, around which the temperature field distribution can be remotely controlled by changing the parameters of the thermal lens. However, due to the lack of negative thermal conductivity, the existing thermal lenses have extremely short focal lengths and cannot be used to remotely control the temperature field around the virtual thermal source/sink. In this study, we theoretically propose a general approach to equivalently realize negative thermal conductivity by elaborately distributed active thermal metasurface (ATMS), then use the proposed ATMS to implement a novel thermal lens with long focal length designed by transformation thermodynamics, and experimentally verify the performance of the designed long-focus thermal lens with measured focal length f=19.8mm for remote heating/cooling. The proposed method expands the scope of the thermal conductivity and open up new ways to realize unprecedented thermal effects with effective negative thermal conductivity, such as "thermal surface plasmon polaritons", thermal superlens, thermal tunneling effect, and thermal invisible gateway

Design and implementation of multi-signal and time-varying neural reconstructions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Several efficient procedures exist to digitally trace neuronal structure from light microscopy, and mature community resources have emerged to store, share, and analyze these datasets. In contrast, the quantification of intracellular distributions and morphological dynamics is not yet standardized. Current widespread descriptions of neuron morphology are static and inadequate for subcellular characterizations. We introduce a new file format to represent multichannel information as well as an open-source Vaa3D plugin to acquire this type of data. Next we define a novel data structure to capture morphological dynamics, and demonstrate its application to different time-lapse experiments. Importantly, we designed both innovations as judicious extensions of the classic SWC format, thus ensuring full back-compatibility with popular visualization and modeling tools. We then deploy the combined multichannel/time-varying reconstruction system on developing neurons in live Drosophila larvae by digitally tracing fluorescently labeled cytoskeletal components along with overall dendritic morphology as they changed over time. This same design is also suitable for quantifying dendritic calcium dynamics and tracking arbor-wide movement of any subcellular substrate of interest.Peer reviewe

MicroRNA-322 inhibits inflammatory cytokine expression and promotes cell proliferation in LPS-stimulated murine macrophages by targeting NF-κB1 (p50)

Correspondence : Hanchuan Dai ([email protected]) Inflammation is the body's normal self-protection mechanism to eliminate pathogens and resist pathogen invasion. The excessive inflammatory response may lead to inflammatory lesions. The mechanisms accounting for inflammation remain hazy. miRNAs have been proposed to have crucial effects on inflammation. In the present study, we reported that lipopolysaccharide (LPS)-stimulation increased the expression levels of inflammatory cytokines and the cell-cycle progression was suppressed in RAW264.7 cells. Meanwhile, the expression of miR-322 was significantly down-regulated after LPS treatment. Bioinformatics predictions revealed a potential binding site of miR-322 in 3 -UTR of NF-κB1 (p50) and it was further confirmed by luciferase assay. Moreover, both the mRNA and protein levels of NF-κB1 (p50) were down-regulated by miR-322 in RAW264.7 cells. Subsequently, we demonstrated that miR-322 mimics decrease in the expression levels of inflammatory cytokines and cell-cycle repression can be rescued following LPS treatment in RAW264.7 cells. The anti-inflammatory cytokines expression including IL-4 and IL-10 were significantly up-regulated. Furthermore, miR-322 could also promote RAW264.7 cells proliferation. These results demonstrate that miR-322 is a negative regulator of inflammatory response by targeting NF-κB1 (p50)

Morphological diversity of single neurons in molecularly defined cell types.

Dendritic and axonal morphology reflects the input and output of neurons and is a defining feature of neuronal types1,2, yet our knowledge of its diversity remains limited. Here, to systematically examine complete single-neuron morphologies on a brain-wide scale, we established a pipeline encompassing sparse labelling, whole-brain imaging, reconstruction, registration and analysis. We fully reconstructed 1,741 neurons from cortex, claustrum, thalamus, striatum and other brain regions in mice. We identified 11 major projection neuron types with distinct morphological features and corresponding transcriptomic identities. Extensive projectional diversity was found within each of these major types, on the basis of which some types were clustered into more refined subtypes. This diversity follows a set of generalizable principles that govern long-range axonal projections at different levels, including molecular correspondence, divergent or convergent projection, axon termination pattern, regional specificity, topography, and individual cell variability. Although clear concordance with transcriptomic profiles is evident at the level of major projection type, fine-grained morphological diversity often does not readily correlate with transcriptomic subtypes derived from unsupervised clustering, highlighting the need for single-cell cross-modality studies. Overall, our study demonstrates the crucial need for quantitative description of complete single-cell anatomy in cell-type classification, as single-cell morphological diversity reveals a plethora of ways in which different cell types and their individual members may contribute to the configuration and function of their respective circuits

Cellular anatomy of the mouse primary motor cortex.

An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted1. Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization. We defined around two dozen projection neuron types in the MOp-ul and derived an input-output wiring diagram, which will facilitate future analyses of motor control circuitry across molecular, cellular and system levels. This work provides a roadmap towards a comprehensive cellular-resolution description of mammalian brain architecture

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

ACCEPTED MANUSCRIPT MicroRNA-322 inhibits inflammatory cytokine expression and promotes cell proliferation in LPS-stimulated murine macrophages by targeting NF-κB1 (P50) BIOSCIENCE REPORTS MicroRNA-322 inhibits inflammatory cytokine expression and promote

Inflammation is the body's normal self-protection mechanism to eliminate pathogens and resist pathogen invasion. The excessive inflammatory response may lead to inflammatory lesions. The mechanisms accounting for inflammation remain hazy. MicroRNAs (miRNAs) have been proposed to have crucial effects on inflammation. In the current study, we reported that lipopolysaccharide (LPS) stimulation increases the expression levels of inflammatory cytokines and the cell cycle progression was suppressed in RAW264.7 cells. Meanwhile, the expression of miR-322 was significantly downregulated after LPS treated. Bioinformatics predictions revealed a potential binding site of miR-322 in 3′-untranslated region (3′-UTR) of and it was further confirmed by luciferase assay. Moreover, both the mRNA and protein levels of NF-κB1 (P50) were downregulated by miR-322 in RAW264.7. Subsequently, we demonstrate that miR-322 mimics decrease the expression levels of inflammatory cytokines and cell cycle repression can be rescued following LPS treated in RAW264.7 cells. The anti-inflammatory cytokines expression including IL-4 and IL-10 were significant up-regulation. Furthermore, miR-322 also could promote RAW264.7 cells proliferation. These results demonstrate that miR-322 is a negative regulator of inflammatory response by targeting NF-κB1 (P50). Abstract Inflammation is the body's normal self-protection mechanism to eliminate pathogens and resist pathogen invasion. The excessive inflammatory response may lead to inflammatory lesions. The mechanisms accounting for inflammation remain hazy. MicroRNAs (miRNAs) have been proposed to have crucial effects on inflammation. In the current study, we reported that lipopolysaccharide (LPS) stimulation increases the expression levels of inflammatory cytokines and the cell cycle progression was suppressed in RAW264.7 cells. Meanwhile, the expression of miR-322 was significantly downregulated after LPS treated. Bioinformatics predictions revealed a potential binding site of miR-322 in 3′-untranslated region (3′-UTR) of NF-κB1 (P50) and it was further confirmed by luciferase assay. Moreover, both the mRNA and protein levels of NF-κB1 (P50) were downregulated by miR-322 in RAW264.7. Subsequently, we demonstrate that miR-322 mimics decrease the expression levels of inflammatory cytokines and cell cycle repression can be rescued following LPS treated in RAW264.7 cells. The anti-inflammatory cytokines expression including IL-4 and IL-10 were significant up-regulation. Furthermore, miR-322 also could promote RAW264.7 cells proliferation. These results demonstrate that miR-322 is a negative regulator of inflammatory response by targeting NF-κB1 (P50)

L-Citrulline Supplementation Restrains Ferritinophagy-Mediated Ferroptosis to Alleviate Iron Overload-Induced Thymus Oxidative Damage and Immune Dysfunction

L-citrulline (L-cit) is a key intermediate in the urea cycle and is known to possess antioxidant and anti-inflammation characteristics. However, the role of L-cit in ameliorating oxidative damage and immune dysfunction against iron overload in the thymus remains unclear. This study explored the underlying mechanism of the antioxidant and anti-inflammation qualities of L-cit on iron overload induced in the thymus. We reported that L-cit administration could robustly alleviate thymus histological damage and reduce iron deposition, as evidenced by the elevation of the CD8+ T lymphocyte number and antioxidative capacity. Moreover, the NF-κB pathway, NCOA4-mediated ferritinophagy, and ferroptosis were attenuated. We further demonstrated that L-cit supplementation significantly elevated the mTEC1 cells’ viability and reversed LDH activity, iron levels, and lipid peroxidation caused by FAC. Importantly, NCOA4 knockdown could reduce the intracellular cytoplasmic ROS, which probably relied on the Nfr2 activation. The results subsequently indicated that NCOA4-mediated ferritinophagy was required for ferroptosis by showing that NCOA4 knockdown reduced ferroptosis and lipid ROS, accompanied with mitochondrial membrane potential elevation. Intriguingly, L-cit treatment significantly inhibited the NF-κB pathway, which might depend on restraining ferritinophagy-mediated ferroptosis. Overall, this study indicated that L-cit might target ferritinophagy-mediated ferroptosis to exert antioxidant and anti-inflammation capacities, which could be a therapeutic strategy against iron overload-induced thymus oxidative damage and immune dysfunction

Train timetabling with dynamic and random passenger demand: A stochastic optimization method

Considering the dynamics and randomness of passenger demand, this paper investigates a train timetabling problem in the stochastic environment for an urban rail transit system. With the scenario-based representation of passenger distribution, an integer nonlinear programming (INLP) model is first formulated to simultaneously optimize the total number of train services, headway settings and speed profile selection decision during the planning time horizon, in which the expected total service cost is treated as the objective function. Through an analysis of the features of the nonlinear constraints, a reformulation method is proposed to develop an equivalent integer linear programming (ILP) model that can be easily solved by commercial software. Moreover, a variable neighborhood search algorithm is developed to find the approximate optimal solutions for large-scale problems within the tolerable computing time. Finally, two sets of numerical experiments, with the operation environments of a simple urban rail transit line and Fuzhou Metro Line 1, are implemented to verify the solution quality and effectiveness of the proposed methods