Background: Thrombocytopenia has long been considered an important complication of chemotherapy and radiotherapy, which severely limits the effectiveness of cancer treatment and the overall survival of patients. However, clinical treatment options are extremely limited so far. Ruxolitinib is a potential candidate. Methods: The impact of ruxolitinib on the differentiation and maturation of K562 and Meg-01 cells megakaryocytes (MKs) was examined by flow cytometry, Giemsa and Phalloidin staining. A mouse model of radiation-injured thrombocytopenia (RIT) was employed to evaluate the action of ruxolitinib on thrombocytopoiesis. Network pharmacology, molecular docking, drug affinity responsive target stability assay (DARTS), RNA sequencing, protein blotting and immunofluorescence analysis were applied to explore the targets and mechanisms of action of ruxolitinib. Results: Ruxolitinib can stimulate MK differentiation and maturation in a dose-dependent manner and accelerates recovery of MKs and thrombocytopoiesis in RIT mice. Biological targeting analysis showed that ruxolitinib binds directly to Toll Like Receptor 2 (TLR2) to activate Rac1/cdc42/JNK, and this action was shown to be blocked by C29, a specific inhibitor of TLR2. Conclusions: Ruxolitinib was first identified to facilitate MK differentiation and thrombocytopoiesis, which may alleviate RIT. The potential mechanism of ruxolitinib was to promote MK differentiation via activating the Rac1/cdc42/JNK pathway through binding to TLR2.
In perspective of scoring criteria, topic settings, and testing emphases, this paper, by comparing the writing task of TOEFL and TEM-8, tried to analyze cultural differences reflected in those two exams, and to put forth some suggestions in English teaching of higher education in China. Based on the research, Chinese higher education on English should strike balance between linguistic foundation and comprehensive ability, autonomous learning and class teaching, and cultural competence and language competence.
Technology has normalised education and promoted teaching and learning activities. However, not all teachers effectively integrate technology into their instruction. Prior studies indicate that teacher knowledge impacts such integration. This study examines technology use among teachers teaching Chinese as a foreign language in Australian secondary schools. Specially, it investigates (a) what teacher knowledge affects technology, (b) how CFL perceive their knowledge, and (c) how to effectively develop teacher knowledge. The findings suggest that technological knowledge (TK) strongly influences CFL instructors’ technology use, and these instructors were more confident in their non-technological knowledge than their technology-related knowledge. The finding regarding relationships between knowledge constructs should shed light on knowledge development for teacher education. Hence, this study contributes to teacher training in Australian secondary schools.
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