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Conceptual models are built to depict and analyze complex systems. They are made of concepts and relationships among these concepts. In a particular domain, conceptual models are helpful for different stakeholders to reach a clear and unified view of domain problems. However, the process of building conceptual models is time-consuming, tedious, and expertise required. To improve the efficiency of the building process, this paper proposes a configurable semantic-based (semi-) automatic conceptual model transformation methodology (SbACMT) that tries to reuse existing conceptual models to generate new models. SbACMT contains three parts: (i) a configurable semantic relatedness computing method building on the structured linguistic knowledge base "ConceptNet" (SRCM-CNet), (ii) a specific meta-model, which follows the Ecore standard, defines the rules of applying SRCM-CNet to different conceptual models to automatically detect transformation mappings, and (iii) a multistep matching and transformation process that employs SRCM-CNet. A case study is carried out to detail the working mechanism of SbACMT. Furthermore, through a systematically analysis of this case study, we validate the performance of SbACMT. We prove that SbACMT can support the automatic transformation process of conceptual models (e.g., class diagrams). The scalability of SbACMT can be improved by adapting the meta-model and predefined syntax transformation rules. [ABSTRACT FROM AUTHOR]

The mechanistic target of rapamycin complex 1 (mTORC1) plays a crucial role in controlling cell growth and homeostasis. Deregulation of mTOR signaling is frequently observed in some cancers, making it an attractive drug target for cancer therapy. Although mTORC1 inhibitor rapalog-based therapy has shown positive results in various pre-clinical animal cancer studies, tumors rebound upon treatment discontinuation. Moreover, several recent clinical trials showed that the mTORC1 inhibitors rapamycin and rapalog only reduce the capacity for cell proliferation without promoting cell death, consistent with the concept that rapamycin is cytostatic and reduces disease progression but is not cytotoxic. It is imperative that rapamycin-regulated events and additional targets for more effective drug combinations be identified. Here, we report that rapamycin treatment promotes a compensatory increase in transglutaminase 2 (TGM2) levels in mTORC1-driven tumors. TGM2 inhibition potently sensitizes mTORC1-hyperactive cancer cells to rapamycin treatment, and a rapamycin-induced autophagy blockade inhibits the compensatory TGM2 upregulation. More importantly, tumor regression was observed in MCF-7-xenograft tumor-bearing mice treated with both mTORC1 and TGM2 inhibitors compared with those treated with either a single inhibitor or the vehicle control. These results demonstrate a critical role for the compensatory increase in transglutaminase 2 levels in promoting mTORC1 inhibitor resistance and suggest that rational combination therapy may potentially suppress cancer therapy resistance. [ABSTRACT FROM AUTHOR]

Simple Summary: Paper mulberry (PM) is an unconventional protein feed material, and silage is its main processing method. The present study aimed to investigate the health benefits and meat quality of supplementing Yangzhou geese with paper mulberry silage. Results indicated that paper mulberry silage supplementation had a promotional effect on the growth of Yangzhou geese, the sensory quality of the breast muscles improved, and the nutritional quality enhanced. Untargeted metabolomics analysis demonstrated that PM treatment enhanced guanidinoacetic acid levels in breast muscles and facilitated the metabolism of amino acids and the role of substances in lipid antioxidant pathways. Consequently, paper mulberry could be considered to be a novel protein feed option capable for geese. There have been few investigations into the health benefits and meat quality of supplementing Yangzhou geese with paper mulberry silage. One hundred and twenty 28-day-old Yangzhou geese were selected for the experiment and randomly divided into two groups: a control group (CON) and a paper mulberry silage group (PM), with six replicates in each group. The experiment lasted for a total of 6 weeks. The experiment found that compared with CON, PM had a promoting effect on the average daily weight gain of Yangzhou geese (p = 0.056). Sensory and nutritional analysis of breast muscles revealed a decrease in a* value (p < 0.05) and an increase in protein content (p < 0.05) following PM treatment. Through untargeted metabolomics analysis of breast muscle samples, it was found that 11 different metabolites, including guanidinoacetic acid and other substances, had a positive effect on amino acid metabolism and lipid antioxidant pathways of PM treatment. Overall, the strategy of feeding Yangzhou geese with paper mulberry silage is feasible, which can improve the sensory quality and nutritional value of goose meat. The experiment provides basic data for the application form of goose breeding, so exploring the impact of substances within paper mulberry on goose meat should be focused on in the future. [ABSTRACT FROM AUTHOR]

• Microplastics activate the NF-κB signaling pathway in the intestinal tissue of carp. • This study identifies, for the first time, microplastics induce ferroptosis in carp. • Intestinal inflammatory injury induced by microplastics in carp. Microplastics (MPs), a new class of pollutant that threatens aquatic biodiversity, are becoming increasingly prevalent around the world. Fish growth may be severely inhibited by microplastics, resulting in severe mortality. Exposure to microplastics increases the likelihood of intestinal injuries, but the underlying mechanisms remain equivocal. The objective of this study was to investigate the potential toxic mechanisms underlying microplastic-induced intestinal injury in fish and to assist researchers in identifying novel therapeutic targets. In this study, a model of carp exposed to microplastics was established successfully. Histological observation showed that exposure to polyethylene microplastics caused damage to the intestinal mucosal surface and a significant increase in goblet cells, which aggregated on the surface of the mucosa. The mucosal layer was observed to fall off. Lymphocytes in the intestinal wall proliferated and aggregated. TUNEL staining showed that apoptosis occurred in the group exposed to microplastics. The qPCR results showed that the expression of Ferroptosis apoptotic factors COX-2 and ACSL4 was upregulated, while the expression of TFRC, FIH1, SLC7A11, and GPX4 was downregulated. The NF-κB pathway (p-p65, IκBα), inflammatory cytokines (TNF-α, IL-8, IL-6) and apoptosis genes (Bax, Caspase3) were upregulated. Semi-quantitative detection of related proteins by Western blotting was consistent with the gene expression results. In addition, the ELISA assay showed that lipid peroxidation and inflammatory cytokines (TNF-α, IL-1β, IL-6) were increased in the microplastic exposed group. To conclude, lipid peroxidation induced by microplastics activates the NF-κB pathway and causes ferroptosis, ultimately resulting in intestinal damage and cellular apoptosis. [ABSTRACT FROM AUTHOR]