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The colon is the largest compartment of the immune system, with innate immune cells exposed to antigens in the environment. However, the mechanisms by which the innate immune system is instigated are poorly defined in colorectal cancer (CRC). Here, a population of CD16+ neutrophils that specifically accumulate in CRC tumor tissues by imaging mass cytometry (IMC), immune fluorescence, and flow cytometry, which demonstrated pro‐tumor activity by disturbing natural killer (NK) cells are identified. It is found that these CD16+ neutrophils possess abnormal cholesterol accumulation due to activation of the CD16/TAK1/NF‐κB axis, which upregulates scavenger receptors for cholesterol intake including CD36 and LRP1. Consequently, these region‐specific CD16+ neutrophils not only competitively inhibit cholesterol intake of NK cells, which interrupts NK lipid raft formation and blocks their antitumor signaling but also release neutrophil extracellular traps (NETs) to induce the death of NK cells. Furthermore, CD16‐knockout reverses the pro‐tumor activity of neutrophils and restored NK cell cytotoxicity. Collectively, the findings suggest that CRC region‐specific CD16+ neutrophils can be a diagnostic marker and potential therapeutic target for CRC. [ABSTRACT FROM AUTHOR]

This study characterized four cholesterol transport-related genes, namely, lcat, acat1, acat2, and mttp, in juvenile tiger puffer in terms of tissue distribution (eye, heart, brain, skin, liver, spleen, muscle, and intestine) and nutritional regulation. Three feeding trials were conducted: (i) using diets with different cholesterol levels (0.11%, 0.65%, 1.10%, 2.32%, and 4.59% of dry matter); (ii) using diets with different lipid levels (8.05%, 12.02%, and 16.36% of dry matter); and (iii) a 1-month starvation experiment with different sampling times (Days 1, 4, 9, 16, and 31). The lcat, acat1, and acat2 were the most abundantly expressed in the liver, while mttp was the most abundantly expressed in the intestine. The lcat had a medium expression level in the muscle and skin but the lowest expression level in the spleen and intestine. The acat1 and acat2 had similar tissue distribution patterns, except that acat2 had a lower expression level in the heart but a higher level in the intestine than acat1. The mttp had medium expression levels in the liver and spleen but had the lowest level in the eye and skin. Different dietary cholesterol levels did not significantly affect the expression of these cholesterol transport genes in the liver and intestine, except that higher cholesterol levels (1.10%–4.59%) significantly downregulated the acat2 expression in the liver. Dietary lipid levels also had a mild influence on the hepatic expression of these genes, except that the diet with 12.02% lipid resulted in significantly higher acat1 expression than the one with 16.36% lipid. The starvation time significantly affected the hepatic expression of these genes. Long-term starvation (16 and 31 days) generally upregulated the hepatic gene expression of lcat, acat1, and mttp but generally downregulated that of acat2. This study provided preliminary knowledge about the tissue distribution and nutritional regulation of cholesterol transport-related genes in marine teleost. [ABSTRACT FROM AUTHOR]

Simple Summary: In some fish farming practices, cholesterol has been used as a feed additive for growth stimulation. Therefore, it is important to increase our knowledge and experience about dietary cholesterol effects on fish. This study provides useful information for the application of cholesterol in fish diets by analyzing the muscle lipidomics changes in turbot and tiger puffer in response to dietary cholesterol supplementation. Exogenous cholesterol has been supplemented into aqua-feeds due to the reduced proportions of fishmeal and fish oil. This study aimed to investigate the effects of dietary cholesterol supplementation on the muscle lipidomics of two marine fish species, turbot and tiger puffer. A 70-day feeding trial was conducted, where two low-fishmeal diets supplemented with 0 or 1% cholesterol were used. The lipidomic analysis with targeted tandem mass spectrometry showed that, in turbot, a total of 49 individual lipids exhibited significant differences in their abundance in response to dietary cholesterol, whereas the number was 30 for tiger puffer. Dietary cholesterol up-regulated the abundance of cholesterol and cholesterol ester in both species. In turbot, the dietary cholesterol also increased the abundance of triacylglycerol and acylcarnitine, whereas in tiger puffer, it primarily regulated the abundance of phospholipids and BMP. This was the first time the responses of marine fish muscle lipidomics to dietary cholesterol supplementation have been investigated. [ABSTRACT FROM AUTHOR]