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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide. Significantly activated uridine nucleotide and fatty acid metabolism in HCC cells promote malignant proliferation and immune evasion. Herein, it is demonstrated that the tripartite motif 65 (TRIM65) E3 ubiquitin‐protein ligase, O‐GlcNAcylated via O‐GlcNAcylation transferase, is highly expressed in HCC and facilitated metabolic remodeling to promote the accumulation of products related to uracil metabolism and palmitic acid, driving the progression of HCC. Mechanistically, it is showed that TRIM65 mediates ubiquitylation at the K44 residue of neurofibromatosis type 2 (NF2), the key protein upstream of classical Hippo signaling. Accelerated NF2 degradation inhibits yes‐associated protein 1 phosphorylation, inducing aberrant activation of related metabolic enzyme transcription, and orchestrating metabolic and immune advantages. In conclusion, these results reveal a critical role for the TRIM family molecule TRIM65 in supporting HCC cell survival and highlight the therapeutic potential of targeting its E3 ligase activity to alter the regulation of proteasomal degradation. [ABSTRACT FROM AUTHOR]

To maintain a reasonable sediment regulation system in the Loess Plateau, it is critical to determine the effects of check dam construction on sediment production and topographic changes. An indoor simulation experiment was conducted to investigate sediment production at the outlet section of the gully and micro‐topographic changes within the channel before and after dam construction. The results showed that check dam significantly affected the run‐off and sediment transport processes in the watershed. Specifically, the cross‐sectional morphology index (η) and the width‐depth ratio increased by 10.23% and 40.44%, respectively, while sediment content and particle size decreased by 39.29% and 18.58%, respectively. Additionally, the relative importance of section parameters and micro‐topographic parameters that affect sediment production rate and particle size was ranked using the random forest algorithm. The roughness after check dam construction was identified as a relatively important topographic factor affecting sediment production and particle selection by erosion. These findings provide valuable information for future check dam construction and development in the Loess Plateau region. [ABSTRACT FROM AUTHOR]

Ultrafine‐grained microstructure and face center cubic (FCC) phase are produced in the pure titanium foils through asymmetrical rolling (ASR) to explore the mechanical properties of pure titanium foils with different thicknesses. Herein, the grain refinement process and phase transformation behavior are systematically investigated. The grain refinement process can be described as: 1) coarse equiaxed grains are elongated along RD due to the compressive strain and shear strain caused by the ASR process. 2) elongated grains are split into thin laths and subgrains by dislocation walls under greater strain. 3) thin laths and subgrains are further refined and ultrafine‐grained microstructures are obtained. In addition, hexagonal close‐packed (HCP)‐FCC phase transformation is also discovered during the ASR process. The orientation relationship between the HCP and FCC phases is determined as [0001]HCP//[001]FCC, (101_0)HCP//(2_20)FCC and the phase transformation is caused by Shockley partial dislocation with Burgers vector 1/6[110]2_ gliding on each (101_0) plane. Uniaxial tensile tests on heat‐treated pure titanium foils of different thicknesses show a size effect on tensile properties. As the thickness decreases, tensile strength and elongation are reduced, with fewer/single‐layer equiaxed grains at the section of the specimen. [ABSTRACT FROM AUTHOR]

Damaged skin cannot prevent harmful bacteria from invading tissues, causing infected wounds and even serious tissue damage. Traditional treatments can not only kill pathogenic bacteria, but also suppress the growth of beneficial bacteria, thus destroying the balance of the damaged skin microbial ecosystem. Here, a living bacterial hydrogel scaffold is reported that accelerates infected wound healing through beneficial bacteria secreting antibacterial substances. Lactobacillus reuteri, a common probiotic, is encapsulated in hydrogel microspheres by emulsion polymerization and further immobilized in a hydrogel network by covalent cross‐linking of methacrylate‐modified hyaluronic acid. Owing to light‐initiated crosslinking, the hydrogel dressing can be generated in situ at the wound site. This hydrogel scaffold not only protects bacteria from immune system attack, but also prevents bacteria from escaping into the local environment, thus avoiding potential threats. Both in vitro and in vivo experiments show that it has excellent ability against harmful bacteria and anti‐inflammatory capabilities, promoting infected wound closure and new tissue regeneration. This work may open up new avenues for the application of living bacteria in the clinical management of infected wounds. [ABSTRACT FROM AUTHOR]

Tumor metastasis is the most common cause of death and poor prognosis for cancer patients. Therapeutics that prevent tumor metastasis are the key to prolonging the lifespan of cancer patients. Cancer stem cells are believed to be critical in the metastatic process. Recently, drug screening for cancer stem cells reports that antipsychotic drugs displayed potential anticancer activity. Thioridazine, one of the antipsychotic drugs for dopamine receptors (DRs), is shown to induce the differentiation of cancer stem cells in leukemic disease and breast cancer, but it is not known if this drug would affect liver cancer. In this study, expression of DR5 was higher in tumors than in nontumor adjacent tissues, while DR1 was lower in human hepatocellular carcinoma (HCC) than those in the adjacent tissues. Other DRs were very low or undetectable. Treatment of HCC cells with thioridazine displays a dose-dependent response in HCC cell lines SNU449, LM3, and Huh7. Thioridazine treatment reduced cell viability and sphere formation of HCC cell lines through induction of G0/G1 cell cycle arrest and suppression of stemness genes CD133, OCT4, and EpCam. It also inhibited cell migration via suppression of epithelial-mesenchymal transition (EMT)-related genes such as twist2 and E-cadherin. Thioridazine-pretreated LM3 cells decreased the capacity of tumorigenesis in nude mice. Taken together, our data suggest that thioridazine may have the potential role in treatment of HCC.