Histone deacetylases (HDACs) 1 and 2 share a high degree of homology and coexist within the same protein complexes. Despite their close association, each possesses unique functions. We show that the upregulation of HDAC2 in colorectal cancer occurred early at the polyp stage, was more robust and occurred more frequently than HDAC1. Similarly, while the expression of HDACs1 and 2 were increased in cervical dysplasia and invasive carcinoma, HDAC2 expression showed a clear demarcation of high-intensity staining at the transition region of dysplasia compared to HDAC1. Upon HDAC2 knockdown, cells displayed an increased number of cellular extensions reminiscent of cell differentiation. There was also an increase in apoptosis, associated with increased p21Cip1/WAF1 expression that was independent of p53. These results suggest that HDACs, especially HDAC2, are important enzymes involved in the early events of carcinogenesis, making them candidate markers for tumor progression and targets for cancer therapy.

Hydrogels find important roles in biomedicine, wearable electronics, and soft robotics, but their mechanical properties are often unsatisfactory. Conventional tough hydrogel designs are based on hydrophilic networks with sacrificial bonds, while the incorporation of hydrophobic polymers into hydrogels is less well understood. In this work, a hydrogel toughening strategy is demonstrated by introducing a hydrophobic polymer as reinforcement. Semicrystalline hydrophobic polymer chains are “woven” into a hydrophilic network via entropy‐driven miscibility. In‐situ‐formed sub‐micrometer crystallites stiffen the network, while entanglements between hydrophobic polymer and hydrophilic network enable large deformation before failure. The hydrogels are stiff, tough, and durable at high swelling ratios of 6–10, and the mechanical properties are tunable. Moreover, they can effectively encapsulate both hydrophobic and hydrophilic molecules.

Receptor for Activated C Kinase 1 (RACK1) is a versatile protein involves in multiple biological processes. In a previous study by Zhao et al., hepatic RACK1 deletion in mice led to an inhibition of autophagy, blocked autophagy-dependent lipolysis and caused steatosis. Using the same mouse model (RACK1hep-/-), we revealed new roles of RACK1 in maintaining bile acid homeostasis and hepatic glucose uptake, which further affected circulatory lipid and glucose level. To be specific, even under hepatic steatosis, the plasma lipids were generally reduced in RACK1hep-/- mouse, which was due to the suppression of intestinal lipid absorption. Accordingly, a decrease of total bile acid level was found in RACK1hep-/- livers, gallbladders and small intestine tissues, and specific decrease of 12-hydroxylated bile acids was detected by LC-MS. Consistently, reduced expression of CYP8B1 was found. A decrease of hepatic glycogen storage was also observed, which might be due to the inhibited glucose uptake by GLUT2 insufficiency. Interestingly, RACK1-KO-inducing hepatic steatosis did not raise insulin resistance (IR), nor IR-inducing factors like ER stress and inflammation. In summary, this study uncovers that hepatic RACK1 might be required in maintaining bile acid homeostasis and glucose uptake in hepatocytes. This study also provides an additional case of hepatic steatosis disassociation with insulin resistance.

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