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Brown adipose tissue (BAT), as the main site of adaptive thermogenesis, exerts beneficial metabolic effects on obesity and insulin resistance. BAT has been previously assumed to contain a homogeneous population of brown adipocytes. Utilizing multiple mouse models capable of genetically labeling different cellular populations, as well as single-cell RNA sequencing and 3D tissue profiling, we discovered a brown adipocyte subpopulation with low thermogenic activity coexisting with the classical high-thermogenic brown adipocytes within the BAT. Compared with the high-thermogenic brown adipocytes, these low-thermogenic brown adipocytes had substantially lower Ucp1 and Adipoq expression, larger lipid droplets, and lower mitochondrial content. Functional analyses showed that, unlike the high-thermogenic brown adipocytes, the lowthermogenic brown adipocytes have markedly lower basal mitochondrial respiration, and they are specialized in fatty acid uptake. Upon changes in environmental temperature, the 2 brown adipocyte subpopulations underwent dynamic interconversions. Cold exposure converted low-thermogenic brown adipocytes into high-thermogenic cells. A thermoneutral environment had the opposite effect. The recruitment of high-thermogenic brown adipocytes by cold stimulation is not affected by high-fat diet feeding, but it does substantially decline with age. Our results revealed a high degree of functional heterogeneity of brown adipocytes., Introduction Brown adipose tissue (BAT) is a thermogenic organ that is thought to play an important role in human energy homeostasis (1-3). Upon activation, brown adipocytes within the BAT can [...]

The application of plant fiber‐reinforced epoxy plastic is severely limited by its relatively low mechanical properties, especially for its brittleness and weak interlaminar properties. The physical and mechanical properties in both nano‐ and macro‐scales of polyurethane/epoxy interpenetration networks were deeply investigated through dynamic mechanical analysis, atomic force microscope and the tensile tests. The atomic force microscope analysis shows that proper amount of polyurethane and evenly distribution could improve the mechanical properties of the resin cast due to the polyurethane/epoxy interpenetrating networks fix the phase zone and increases the strength and stiffness of the system and this was proven with macroscale tensile tests. Moreover, it is impressive to notice that with addition of 15 wt% of polyurethane into epoxy, the initial fracture toughness of its corresponding composite exhibits 48% enhancement. The results in this study indicate that polyurethane/epoxy interpenetration networks show positive effect on improving the interfacial and interlaminar properties of plant fiber reinforced composites. [ABSTRACT FROM AUTHOR]

Organoid tumor models have emerged as a powerful tool in the fields of biology and medicine as such 3D structures grown from tumor cells recapitulate better tumor characteristics, making these tumoroids unique for personalized cancer research. Assessment of their functional behavior, particularly protein secretion, is of significant importance to provide comprehensive insights. Here, a label-free spectroscopic imaging platform is presented with advanced integrated optofluidic nanoplasmonic biosensor that enables real-time secretion analysis from single tumoroids. A novel two-layer microwell design isolates tumoroids, preventing signal interference, and the microarray configuration allows concurrent analysis of multiple tumoroids. The dual imaging capability combining time-lapse plasmonic spectroscopy and bright-field microscopy facilitates simultaneous observation of secretion dynamics, motility, and morphology. The integrated biosensor is demonstrated with colorectal tumoroids derived from both cell lines and patient samples to investigate their vascular endothelial growth factor A (VEGF-A) secretion, growth, and movement under various conditions, including normoxia, hypoxia, and drug treatment. This platform, by offering a label-free approach with nanophotonics to monitor tumoroids, can pave the way for new applications in fundamental biological studies, drug screening, and the development of therapies., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Immune composition within the tumor microenvironment (TME) plays a central role in the propensity of cancer to metastasize and to respond to therapy. Previous studies suggested that the metastatic TME is immune suppressed. However, limited accessibility to multiple metastatic sites within patients has made assessment of the immune TME in the context of multi-organ metastases difficult. We utilized a rapid postmortem tissue collection protocol to assess immune composition in numerous sites of breast cancer metastasis and paired tumor-free tissues. Metastases were found to have comparable immune cell densities and composition to paired tumor-free tissues of the same organ type. In contrast, immune cell densities in both metastatic and tumor-free tissues were significantly different between organ types, with lung immune infiltration consistently greater than liver. These immune profiling results were consistent between both flow cytometry and multiplex immunofluorescence-based spatial analysis. Furthermore, we found granulocytes were a predominant tumor-infiltrating immune cell in both lung and liver metastases and these granulocytes made up the majority of PD-L1-expressing cells in many tissue sites. We also identified distinct potential mechanisms of immunosuppression in lung and liver metastases, with lung having increased expression of PD-L1+ antigen-presenting cells and liver having higher numbers of activated regulatory T cells and HLA-DRlow monocytes. Together these results demonstrate that immune contexture of metastases is dictated by organ type, and that immunotherapy strategies may benefit from unique tailoring to tissue-specific features of the immune TME.