The structural evolution of dielectric elastomer induced by pre-strain is a complex, multi-scale process that poses a significant challenge to a deep understanding of the effect of pre-strain. Through simulation results, we identify the variation in the dielectric constant and multi-scale (electronic structure, molecular chain conformation, and aggregation structure) response of poly(methyl acrylate). As the pre-strain increases, the dielectric constant initially rises (below 200% pre-strain) and then declines (above 200% pre-strain).
View Article and Find Full Text PDFA wide variety of systemic pathologies, including infectious and autoimmune diseases, are accompanied by joint pain or inflammation, often mediated by circulating immune complexes (ICs). How such stimuli access joints and trigger inflammation is unclear. Whole-mount synovial imaging revealed PV1 fenestrated capillaries at the periphery of the synovium in the lining-sublining interface.
View Article and Find Full Text PDFThe liver macrophage population comprises resident Kupffer cells (KCs) and monocyte-derived macrophages with distinct pro- or anti-inflammatory properties that affect the severity and course of liver diseases. The mechanisms underlying macrophage differentiation and functions in metabolic dysfunction-associated steatotic liver disease and/or steatohepatitis (MASLD/MASH) remain mostly unknown. Using single-cell RNA sequencing (scRNA-seq) and fate mapping of hepatic macrophage subpopulations, we unraveled the temporal and spatial dynamics of distinct monocyte and monocyte-derived macrophage subsets in MASH.
View Article and Find Full Text PDFLangerhans cells (LCs) are distinct among phagocytes, functioning both as embryo-derived, tissue-resident macrophages in skin innervation and repair and as migrating professional antigen-presenting cells, a function classically assigned to dendritic cells (DCs). Here, we demonstrate that both intrinsic and extrinsic factors imprint this dual identity. Using ablation of embryo-derived LCs in the murine adult skin and tracking differentiation of incoming monocyte-derived replacements, we found intrinsic intraepidermal heterogeneity.
View Article and Find Full Text PDFPhotodiagnosis Photodyn Ther
October 2024
Background: Photodynamic therapy (PDT) has been emerging as a promising treatment for unresectable cholangiocarcinoma (CCA). A number of experiments have demonstrated that PDT could enhance antitumor immunity significantly. However, the impact of PDT on peripheral immune system for unresectable CCA remains unclear.
View Article and Find Full Text PDFTumor-associated macrophages (TAMs) are a heterogeneous population of cells whose phenotypes and functions are shaped by factors that are incompletely understood. Herein, we asked when and where TAMs arise from blood monocytes and how they evolve during tumor development. We initiated pancreatic ductal adenocarcinoma (PDAC) in inducible monocyte fate-mapping mice and combined single-cell transcriptomics and high-dimensional flow cytometry to profile the monocyte-to-TAM transition.
View Article and Find Full Text PDFConventional dendritic cells (cDC) are antigen-presenting cells comprising cDC1 and cDC2, responsible for priming naive CD8 and CD4 T cells, respectively. Recent studies have unveiled cDC2 heterogeneity and identified various cDC2 progenitors beyond the common DC progenitor (CDP), hinting at distinct cDC2 lineages. By generating Cd300cR26 reporter mice, we identified a bone marrow pro-cDC2 progenitor exclusively generating cDC2 in vitro and in vivo.
View Article and Find Full Text PDFAcute stroke triggers extensive changes to myeloid immune cell populations in the brain that may be targets for limiting brain damage and enhancing repair. Immunomodulatory approaches will be most effective with precise manipulation of discrete myeloid cell phenotypes in time and space. Here, we investigate how stroke alters mononuclear myeloid cell composition and phenotypes at single-cell resolution and key spatial patterns.
View Article and Find Full Text PDFThe marine bacterium sp. HNS054 shows promise as a platform for producing natural products. Isolated from a marine sponge, HNS054 possesses several desirable traits for bioengineering: rapid growth, salt tolerance, and compatibility with genetic tools.
View Article and Find Full Text PDFMicroglial reactivity to injury and disease is emerging as a heterogeneous, dynamic, and crucial determinant in neurological disorders. However, the plasticity and fate of disease-associated microglia (DAM) remain largely unknown. We established a lineage tracing system, leveraging the expression dynamics of secreted phosphoprotein 1(Spp1) to label and track DAM-like microglia during brain injury and recovery.
View Article and Find Full Text PDFEosinophils are a group of granulocytes well known for their capacity to protect the host from parasites and regulate immune function. Diverse biological roles for eosinophils have been increasingly identified, but the developmental pattern and regulation of the eosinophil lineage remain largely unknown. Herein, we utilize the zebrafish model to analyze eosinophilic cell differentiation, distribution, and regulation.
View Article and Find Full Text PDFNeutrophils are increasingly recognized as key players in the tumor immune response and are associated with poor clinical outcomes. Despite recent advances characterizing the diversity of neutrophil states in cancer, common trajectories and mechanisms governing the ontogeny and relationship between these neutrophil states remain undefined. Here, we demonstrate that immature and mature neutrophils that enter tumors undergo irreversible epigenetic, transcriptional, and proteomic modifications to converge into a distinct, terminally differentiated dcTRAIL-R1 state.
View Article and Find Full Text PDFTumor-associated macrophages (TAMs) are a heterogeneous population that play diverse functions in tumors. Their identity is determined not only by intrinsic factors, such as origins and transcription factors, but also by external signals from the tumor microenvironment (TME), such as inflammatory signals and metabolic reprogramming. Metabolic reprogramming has rendered TAM to exhibit a spectrum of activities ranging from pro-tumorigenic to anti-tumorigenic, closely associated with tumor progression and clinical prognosis.
View Article and Find Full Text PDFThe percentage of macrophage subpopulations based on their origins in the adult cochlea remains unclear. This study aimed to elucidate the origins of cochlear macrophages during the onset phase and development of auditory function. We used three types of mice: wildtype ICR mice, colony-stimulating factor 1 receptor (Csf1r)-deficient mice, and Ms4a3Cre-Rosa tdTomato (Ms4a3) transgenic mice.
View Article and Find Full Text PDFMyeloid cells are known to suppress antitumour immunity. However, the molecular drivers of immunosuppressive myeloid cell states are not well defined. Here we used single-cell RNA sequencing of human and mouse non-small cell lung cancer (NSCLC) lesions, and found that in both species the type 2 cytokine interleukin-4 (IL-4) was predicted to be the primary driver of the tumour-infiltrating monocyte-derived macrophage phenotype.
View Article and Find Full Text PDFPancreatic ductal adenocarcinoma (PDAC) is a lethal disease with high resistance to therapies. Inflammatory and immunomodulatory signals co-exist in the pancreatic tumour microenvironment, leading to dysregulated repair and cytotoxic responses. Tumour-associated macrophages (TAMs) have key roles in PDAC, but their diversity has prevented therapeutic exploitation.
View Article and Find Full Text PDFAborycin is a type I lasso peptide with a stable interlocked structure, offering a favorable framework for drug development. The aborycin biosynthetic gene cluster from marine sponge-associated sp. HNS054 was cloned and integrated into the chromosome of hosts with different copies.
View Article and Find Full Text PDFKupffer cells (KCs) are localized in liver sinusoids but extend pseudopods to parenchymal cells to maintain their identity and serve as the body's central bacterial filter. Liver cirrhosis drastically alters vascular architecture, but how KCs adapt is unclear. We used a mouse model of liver fibrosis and human tissue to examine immune adaptation.
View Article and Find Full Text PDFConventional dendritic cells (cDCs) are professional antigen-presenting cells that control the adaptive immune response. Their subsets and developmental origins have been intensively investigated but are still not fully understood as their phenotypes, especially in the DC2 lineage and the recently described human DC3s, overlap with monocytes. Here, using LEGENDScreen to profile DC vs.
View Article and Find Full Text PDFOvarian cancer (OC) is an aggressive gynecological tumor usually diagnosed with widespread metastases and ascites. Here, we depicted a single-cell landscape of the OC ecosystem with five tumor-relevant sites, including omentum metastasis and malignant ascites. Our data reveal the potential roles of ascites-enriched memory T cells as a pool for tumor-infiltrating exhausted CD8 T cells and T helper 1-like cells.
View Article and Find Full Text PDFMacrophages are involved in immune defense, organogenesis and tissue homeostasis. Macrophages contribute to the different phases of mammary gland remodeling during development, pregnancy and involution postlactation. Less is known about the dynamics of mammary gland macrophages in the lactation stage.
View Article and Find Full Text PDFCorrect development and maturation of the enteric nervous system (ENS) is critical for survival. At birth, the ENS is immature and requires considerable refinement to exert its functions in adulthood. Here we demonstrate that resident macrophages of the muscularis externa (MMϕ) refine the ENS early in life by pruning synapses and phagocytosing enteric neurons.
View Article and Find Full Text PDFThe recruitment of monocytes and their differentiation into immunosuppressive cells is associated with the low efficacy of preclinical nonconformal radiotherapy (RT) for tumors. However, nonconformal RT (non-CRT) does not mimic clinical practice, and little is known about the role of monocytes after RT modes used in patients, such as conformal RT (CRT). Here, we investigated the acute immune response induced by after CRT.
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