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One of the primary obstacles in current cancer treatments lies in the extensive heterogeneity of genetic and epigenetic changes that occur in each arising tumour. However, an additional challenge persists, as certain types of cancer display shared immune deficiencies in the antigen processing machinery (APM). This includes the downregulation of human leukocyte antigen (HLA) class I molecules, which serve as peptide antigen receptors for T lymphocyte recognition that plays a crucial role in killing emerging tumours. Consequently, this contributes to immune escape in metastatic disease. Notably, current cell-based immunotherapies primarily focusing on T lymphocytes and the implementation of immune checkpoint inhibitor modalities have largely ignored the crucial task of reversing immune escape. This oversight may explain the limited success of these approaches becoming more effective cancer immunotherapies. Hence, there is a critical need to prioritize the discovery of new therapeutic candidates that can effectively address immune escape and synergize with evolving immunotherapy strategies. In this context, we identified curcuphenol in a cell-based screen from a library of marine extracts as a chemical entity that reverses the immuneescape phenotype of metastatic cancers. To advance these findings toward clinical efficacy, the present study describes the synthesis of analogues of naturally occurring curcuphenol with enhanced chemical properties and biological efficacy. Here we test the hypothesis that these curcuphenol analogues can evoke the power of the immune system to reduce the growth of metastatic disease in tumour bearing animals. Our findings indicate that these compounds effectively restore the expression of APM genes in metastatic tumours and inhibit the growth of highly invasive tumours in preclinical models, thereby counteracting the common immune evasion phenomenon observed in metastatic cancers. We conclude that cancer immunotherapies capable of boosting APM expression, hold great potential in maximizing the effectiveness of immune blockade inhibitors and eradicating invasive tumours. [ABSTRACT FROM AUTHOR]

Social media influencers (SMIs) are immensely popular and act as cultural gatekeepers for beauty. While advertisers commonly believe that "beauty sells," this study asks (1) what types of beauty do SMIs depict and how does it compare to that portrayed in fashion magazines over thirty years ago? (2) as cultural gatekeepers what cultural values do SMIs depict and how are they related to the types of beauty? And (3) what are Generation Z's (Gen Z) perceptions of the types of beauty depicted by beauty SMIs? These questions are answered through a content analysis of the top-100 beauty influencers and interviews with 20 Gen Z consumers analyzed using Interpretative Phenomenological Analysis The study found that standard beauty ideals are still valuable when used by SMIs, but the weight of each type is more fluid and SMIs can flow between more than one. SMIs are also helping to grow new or nonstandard beauty ideals, categorized as "other." The study proves extant knowledge evolves and adapts to this new revolutionary digital format and highlights future possible paths for the future of Gen Z beauty advertising. [ABSTRACT FROM AUTHOR]

Many natural products that contain basic nitrogen atoms--for example alkaloids like morphine and quinine-have the potential to treat a broad range of human diseases. However, the presence of a nitrogen atom in a target molecule can complicate its chemical synthesis because of the basicity of nitrogen atoms and their susceptibility to oxidation. Obtaining such compounds by chemical synthesis can be further complicated by the presence of multiple nitrogen atoms, but it can be done by the selective introduction and removal of functional groups that mitigate basicity. Here we use such a strategy to complete the chemical syntheses of citrinalin B and cyclopiamine B. The chemical connections that have been realized as a result of these syntheses, in addition to the isolation of both 17-hydroxycitrinalin B and citrinalin C (which contains a bicyclo[2.2.2]diazaoctane structural unit) through carbon-13 feeding studies, support the existence of a common bicyclo[2.2.2]diazaoctane-containing biogenetic precursor to these compounds, as has been proposed previously.

Curcuphenol, a common component of the culinary spices, naturally found in marine invertebrates and plants, has been identified as a novel candidate for reversing immune escape by restoring expression of the antigen presentationmachinery (APM) in invasive cancers, thereby resurrecting the immune recognition of metastatic tumours. Two synthetic curcuphenol analogues, were prepared by informed design that demonstrated consistent induction of APM expression in metastatic prostate and lung carcinoma cells. Both analogues were subsequently found to possess a previously undescribed histone deacetylase (HDAC)-enhancing activity. Remarkably, the H3K27ac ChIPseq analysis of curcuphenol-treated cells reveals that the induced epigenomic marks closely resemble the changes in genome-wide pattern observed with interferon-γ, a cytokine instrumental for orchestrating innate and adaptive immunity. These observations link dietary components to modifying epigenetic programs that modulate gene expression guiding poised immunity. [ABSTRACT FROM AUTHOR]

Genetic and epigenetic events have been implicated in the downregulation of the cellular antigen processing and presentation machinery (APM), which in turn, has been associated with cancer evasion of the immune system. When these essential components are lacking, cancers develop the ability to subvert host immune surveillance allowing cancer cells to become invisible to the immune system and, in turn, promote cancer metastasis. Here we describe and validate the first highthroughput cell-based screening assay to identify chemical extracts and unique chemical entities that reverse the downregulation of APM components in cell lines derived from metastatic tumours. Through the screening of a library of 480 marine invertebrate extracts followed by bioassay-guided fractionation, curcuphenol, a common sesquiterpene phenol derived from turmeric, was identified as the active compound of one of the extracts. We demonstrate that curcuphenol induces the expression of the APM components, TAP-1 and MHC-I molecules, in cell lines derived from both metastatic prostate and lung carcinomas. Turmeric and curcumins that contain curcuphenol have long been utilized not only as a spice in the preparation of food, but also in traditional medicines for treating cancers. The remarkable discovery that a common component of spices can increase the expression of APM components in metastatic tumour cells and, therefore reverse immune-escape mechanisms, provides a rationale for the development of foods and advanced nutraceuticals as therapeutic candidates for harnessing the power of the immune system to recognize and destroy metastatic cancers. [ABSTRACT FROM AUTHOR]

The development of microstructures which combine high total surface area and high porosity is crucial for technologies such as electrocatalysis, electrochromics, and sensors. High deposition rate, composition control of deposition, and low processing temperature to retain active compositions are also desirable. To this end, this study describes combining colloidal sol chemistry with a nonthermal atmospheric pressure dielectric barrier discharge plasma jet to print hybrid inorganic/organic tungsten trioxide/oxalic acid (WO3–x/OA) microspheres. Injection of an aerosol of oxalic acid stabilized colloidal tungstic acid into an atmospheric pressure plasma jet results in the deposition of spherical structures in which the colloid is trapped within a plasma-polymerized organic shell. Subsequent low-temperature sintering produces hierarchical spherical shell-like structures comprising tungsten oxide nanosheets. Alteration of the gas flow rate changes the composition of the deposited material. The method has promise for the general preparation from colloidal precursors of porous materials of controlled morphology and composition with hierarchical microstructures, such as are required for applications in electrochemical devices and sensors which need a high ratio of surface area to volume and connectivity throughout the structure, yet also need a microstructure which is open for rapid exchange of reactants. [ABSTRACT FROM AUTHOR]