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Altogether, we demonstrate the diagnostic value of pHLuc as a bioluminescent reporter for pH variations across the tumor microenvironment. The pHLuc reporter plasmids constructed in this work are available from Addgene.The Graves’ disease is an autoimmune disease highly associated with thyroid cancer. The Graves’ ophthalmopathy (GO) is a special Graves’ disease with inflammatory ophthalmopathy being a typical extrathymic complication. GO is caused by the formation of orbital fat and extraocular muscle fibrosis due to the inflammation of orbital connective tissues. Thus, controlling extraocular muscle fibrosis is critical for the prognosis of GO. The objective of this study is to identify and experimentally validate key genes associated with GO and explore their potential function mechanisms especially on extraocular muscle fibrosis. Specifically, we first created a GO mouse model, and performed RNA sequencing on the extraocular muscles of fibrotic GO mice and controls. SRC was identified as the most significant unstudied differentially expressed gene between GO mice and controls. Thus, we conducted a few in vitro analyses to explore the roles and functions of SRC in GO, for which we selected primary cultured orbital fibroblast (OF) as the in vitro cell line model. It is known that myofibroblast (MFB), which expresses α-SMA, is an important target cell in the process of fibrosis. Our experiment suggests that TGF-β can induce the transformation from OF to MFB, however, the transformation was inhibited by silencing the SRC gene in OF. buy JQ1 In addition, we also inhibited TGF-β/Smad, NF-κB, and PI3K/Akt signaling pathways to analyze the interaction between these pathways and SRC. In conclusion, the silence of SRC in OF can inhibit the transformation from OF to MFB, which might be associated with the interaction between SRC and a few pathways such as TGF-β/Smad, NF-κB, and PI3K/Akt.In the field of skin tissue engineering, the development of physiologically relevant in vitro skin models comprising all skin layers, namely epidermis, dermis, and subcutis, is a great challenge. Increasing regulatory requirements and the ban on animal experiments for substance testing demand the development of reliable and in vivo-like test systems, which enable high-throughput screening of substances. However, the reproducibility and applicability of in vitro testing has so far been insufficient due to fibroblast-mediated contraction. To overcome this pitfall, an advanced 3-layered skin model was developed. While the epidermis of standard skin models showed an 80% contraction, the initial epidermal area of our advanced skin models was maintained. The improved barrier function of the advanced models was quantified by an indirect barrier function test and a permeability assay. Histochemical and immunofluorescence staining of the advanced model showed well-defined epidermal layers, a dermal part with distributed human dermal fibroblasts and a subcutis with round-shaped adipocytes. The successful response of these advanced 3-layered models for skin irritation testing demonstrated the suitability as an in vitro model for these clinical tests only the advanced model classified irritative and non-irritative substances correctly. These results indicate that the advanced set up of the 3-layered in vitro skin model maintains skin barrier function and therefore makes them more suitable for irritation testing.Conventional medical imaging phantoms are limited by simplified geometry and radiographic skeletal homogeneity, which confines their usability for image quality assessment and radiation dosimetry. These challenges can be addressed by additive manufacturing technology, colloquially called 3D printing, which provides accurate anatomical replication and flexibility in material manipulation. In this study, we used Computed Tomography (CT)-based modified PolyJetTM 3D printing technology to print a hollow thorax phantom simulating skeletal morphology of the patient. To achieve realistic heterogenous skeletal radiation attenuation, we developed a novel radiopaque amalgamate constituting of epoxy, polypropylene and bone meal powder in twelve different ratios. We performed CT analysis for quantification of material radiodensity (in Hounsfield Units, HU) and for identification of specific compositions corresponding to the various skeletal structures in the thorax. We filled the skeletal structures with their respective radiopaque amalgamates. The phantom and isolated 3D printed rib specimens were rescanned by CT for reproducibility tests regarding verification of radiodensity and geometry. Our results showed that structural densities in the range of 42-705HU could be achieved. The radiodensity of the reconstructed phantom was comparable to the three skeletal structures investigated in a real patient thorax CT ribs, ventral vertebral body and dorsal vertebral body. Reproducibility tests based on physical dimensional comparison between the patient and phantom CT-based segmentation displayed 97% of overlap in the range of 0.00-4.57 mm embracing the anatomical accuracy. Thus, the additively manufactured anthropomorphic thorax phantom opens new vistas for imaging- and radiation-based patient care in precision medicine.Objective Colorectal cancer is a malignant tumor of the digestive system with high morbidity and mortality. 5-fluorouracil remains a widely used chemotherapeutic drug in the treatment of advanced colorectal cancer, but chemotherapy drugs are prone to develop drug resistance, p53 deletion or mutation is an important reason for the resistance of colorectal cancer cells to 5-fluorouracil. β-elemene has been proved to have the potential of reverse chemotherapy drug resistance, but the mechanism is unknown. This study aimed to investigate the effect of β-elemene to 5-fluorouracil in drug-resistant p53-deficient colorectal cancer cells HCT116p53-/-, and determine the possible molecular mechanism of β-elemene to reverse 5-fluorouracil resistance. Methods The effect of β-elemene on HCT116p53-/- cell activity was detected by Cell counting Kit-8. Cell proliferation was detected by monoclonal plate. The apoptosis was detected by flow cytometry and western blot. The autophagy was detected by western blot, immunofluorescence and transmission electron microscope.