This Account describes a new paradigm, Langmuir-Blodgett (LB) patterning, for large-area patterning with mesostructured features based on the well-established LB technique. This strategy uses a simple fabrication technique to control the alignment, size, shape, and periodicity of self-organized phospholipid monolayer patterns with feature sizes down to 100 nm over surface areas of square centimeters. Because of the anisotropic wetting behavior of the patterns, they can be used as templates to direct the self-assembly of functional molecules and nanocrystals. Furthermore, the chemical patterns can be converted into topographical structures, which can be used to direct cell growth and organize nanocrystals. The mesoscopic structured surfaces described here may serve as a platform in engineering the biological/material interface and constructing biofunctionalized structures and "programmed" systems.
Abstract The γδT‐cells recognize infected or transformed cells. However, unlike αβT‐cells, γδT‐cells are innate‐like immune cells, with no major histocompatibility complex restriction requirements. γδT‐cells are the main population of intestinal intraepithelial lymphocytes (IELs) and are associated with the antitumor immune response, particularly in colorectal cancer (CRC). Although CD8 + T‐cells exhibit dysfunction and even exhaustion in the tumor microenvironment (TME), which contributes to tumor immune escape, whether the same applies to tumor‐infiltrating (TI)‐γδT‐cells is not completely understood. Here, we sought to investigate the expression pattern of inhibitory receptors and functional state of TI‐γδT‐cells, and reveal the features of exhausted TI‐γδT‐cells in the CRC TME. We demonstrated that TI‐γδT‐cells exhibited exhaustion phenotypes and displayed more severe functional exhaustion than TI‐CD8 + T‐cells or NK‐cells in the TME of CRC. In addition, scRNA‐seq analysis of TI‐γδT‐cells revealed three exhausted subsets with remarkable heterogeneity. The presence of three heterogeneous exhausted γδT‐cell (Tex) populations, including Tex prog , Tex tran and Tex term were further confirmed by flow cytometry, on the basis of PD‐1 and TIM‐3 expression. Finally, we revealed that c‐Maf not only contributed to γδT‐cell exhaustion via upregulation of inhibitory receptors, but also involved in the exhaustion of CD8 + T and NK‐cells. c‐Maf may also be an important contributor to γδT‐cell exhaustion in CRC patients. These findings indicated that TI‐γδT‐cells exhibit phenotypic and functional exhaustion in the CRC TME. The revealed features of exhausted TI‐γδT‐cells may provide help for understanding the mechanisms and the association of γδT‐cell exhaustion with tumor development and pathogenesis.
The engulfment and subsequent degradation of apoptotic cells by phagocytes is an evolutionarily conserved process that efficiently removes dying cells from animal bodies during development. Here, we report that clathrin heavy chain (CHC-1), a membrane coat protein well known for its role in receptor-mediated endocytosis, and its adaptor epsin (EPN-1) play crucial roles in removing apoptotic cells in Caenorhabditis elegans. Inactivating epn-1 or chc-1 disrupts engulfment by impairing actin polymerization. This defect is partially suppressed by inactivating UNC-60, a cofilin ortholog and actin server/depolymerization protein, further indicating that EPN-1 and CHC-1 regulate actin assembly during pseudopod extension. CHC-1 is enriched on extending pseudopods together with EPN-1, in an EPN-1-dependent manner. Epistasis analysis places epn-1 and chc-1 in the same cell-corpse engulfment pathway as ced-1, ced-6 and dyn-1. CED-1 signaling is necessary for the pseudopod enrichment of EPN-1 and CHC-1. CED-1, CED-6 and DYN-1, like EPN-1 and CHC-1, are essential for the assembly and stability of F-actin underneath pseudopods. We propose that in response to CED-1 signaling, CHC-1 is recruited to the phagocytic cup through EPN-1 and acts as a scaffold protein to organize actin remodeling. Our work reveals novel roles of clathrin and epsin in apoptotic-cell internalization, suggests a Hip1/R-independent mechanism linking clathrin to actin assembly, and ties the CED-1 pathway to cytoskeleton remodeling.
Abstract Background Heat shock protein 27 (HSP27) and interleukin-17 (IL-17) are important indicators of inflammation. Whether serum HSP27 and IL-17 levels hold predictive value on the prognosis of patients with acute myocardial infarction (AMI) remains unclear. Methods This was a prospective cohort study enrolled 140 patients in the Department of Cardiology of Fujian Provincial Hospital from December 2020 to June 2021, including 40 patients of non-AMI and 100 patients of AMI. The levels of serum HSP27, Phosphorylated HPS27 (pHSP27) and IL-17 were measured by enzyme linked immunosorbent assay. Patients with AMI were followed up. The follow-up endpoint was major adverse cardiovascular events (MACEs), including recurrent angina pectoris, re-admission heart failure, re-admission myocardial infarction, stroke, and death. And follow-up ended on December 31, 2021. Results HSP27, pHSP27 and IL-17 were higher in AMI patients than in non-AMI patients (All P < 0.05). HSP27 level was negatively correlated with troponin I level (r = -0.243, P < 0.05). And there were negative correlations between HSP27, IL-17 and Gensini scores, respectively (r (HSP27) =-0.374, P = 0.002;r (IL−17) = -0.289, P = 0.016). All 100 patients with AMI were followed up. The median follow-up was 8 months. There were 30 cases of MACEs. The area under the receiver operating characteristic curve for the predict of MACEs was higher for joint model (combining HSP27, pHSP27 and IL-17) than for HSP27, pHSP27 and IL-17 alone. Univariate COX regression analysis showed that HSP27 (HR = 0.968, P = 0.01), pHSP27 (HR = 0.972, P = 0.039) and IL-17 (HR = 0.979, P = 0.004) were protective factors for endpoint free survival. HSP27 and IL-17 were associated with MACEs after correction for confounding factors (HR (HSP27) = 0.972, P = 0.39; HR (IL−17) = 0.979, P = 0.004). Conclusion HSP27, pHSP27 and IL-17 were higher in AMI patients than in non-AMI patients. But HSP27, pHSP27 and IL-17 could reduce the occurrence of MACEs in AMI patients.
It has been reported that the adult liver contains hematopoietic stem and progenitor cells (HSPCs), which are associated with long-term hematopoietic reconstitution activity. Hepatic hematopoiesis plays an important role in the generation of cells involved in liver diseases. However, how the progenitors differentiate into functional myeloid cells and lymphocytes in the liver microenvironment remains unknown. In the present study, HSPC transplantation experiments were used to confirm that adult murine liver HSPCs differentiate into both myeloid cells and lymphocytes (preferentially T cells) compared with bone marrow HSPCs. Using a coculture system comprised of kupffer cells and HSPCs, we found that kupffer cells promote adult liver HSPCs to primarily generate T cells and B cells. We then demonstrated that kupffer cells can also promote HSPC expansion. A blockade of intercellular cell adhesion molecule-1 (ICAM-1) in a liver HSPC and kupffer cell coculture system impaired the adhesion, expansion, and differentiation of HSPCs. These results suggest a critical role of kupffer cells in the maintenance and promotion of adult mouse liver hematopoiesis. These findings provide important insight into understanding liver extramedullary hematopoiesis and its significance, particularly under the state of some liver diseases, such as hepatitis, nonalcoholic fatty liver disease (NAFLD), and hepatocellular carcinoma (HCC).
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