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Abstract Background Artemisinin (ART) analogs, such as dihydroartemisinin, arteether, artemether, and artesunate, all featuring an endoperoxide bridge, have demonstrated efficacy against schistosomiasis. Artemisitene (ATT), which contains an additional α, β-unsaturated carbonyl structure, has shown enhanced biological activities. This study aims to evaluate the anti-schistosomaiasis japonica activity of ATT and compare it with ART. Methods We assessed liver inflammation and fibrosis in mice using hematoxylin and eosin staining and Sirius red staining, respectively. RNA sequencing analyzed transcriptomics in female and male Schistosoma japonicum (S. japonicum) adult worms and mice livers, with cytokine profiling and flow cytometry to study immune responses under ART or ATT treatment. Results ATT exhibits a marked reduction in female S. japonicum adult worms and egg numbers, damaging the adult worms’ surface. It also influences the transcription of genes related to cellular anatomical structures. Notably, ATT treatment resulted in significant reductions in liver granuloma size and collagen area, alongside lowering serum levels of glutamic pyruvic and glutamic oxaloacetic transaminase more effectively than ART. Both ART and ATT markedly decreased neutrophil frequency in the liver and elevated eosinophil counts. However, only ATT treatment significantly reduced the M1/M2 and Th1/Th2 indices, indicating a pronounced shift in immune response profiles. ATT-affected host immunity correlated with the extent of liver fibrosis and the count of single males more strongly than ART. Conclusion ATT, as a novel preventive strategy for schistosomiasis japonica in mice, significantly outperforms ART. Graphical Abstract

Mast cell leukemia is a rare and aggressive disease, predominantly with KIT D816V mutation. With poor response to conventional poly-chemotherapy, mast cell leukemia responded to the midostaurin treatment with a 50% overall response rate (ORR), but complete remission rate is approximately 0%. Therefore, the potential mechanisms of midostaurin resistance and the exact impacts of midostaurin on both gene expression profile and mast cell leukemia microenvironment in vivo are essential for design tailored combination therapy targeting both the tumor cells and the tumor microenvironment. Here we report a 59-year-old male mast cell leukemia patient with KIT F522C mutation treated with midostaurin. Single-cell sequencing of peripheral blood and whole exome sequencing (WES) of bone marrow were performed before and 10 months after midostaurin treatment. In accordance with the clinical response, compared to the pretreatment aberration, the decline of mast cells and increase of T-, NK, B-cells in peripheral blood, and the decrease of the KIT F522C mutation burden in bone marrow were observed. Meanwhile, the emergence of RUNX1 mutation, upregulations of genes expression (RPS27A, RPS6, UBA52, RACK1) on tumor cells, and increased frequencies of T and NK cells with TIGIT, CTLA4, and LAG3 expression were observed after midostaurin treatment, predicting the disease progression of this patient. As far as we know, this is the first case reporting the clinical, immunological, and molecular changes in mast cell leukemia patients before and after midostaurin treatment, illustrating the in vivo mechanisms of midostaurin resistance in mast cell leukemia, providing important clues to develop a sequential option to circumvent tumor progression after targeting oncogene addiction and prolong patients’ survival.

Lymphoma is a common and aggressive form of hematopoietic malignancies with diverse clinical and pathological features due to its heterogeneity. Although the current immunochemotherapeutic regimens improve clinical outcomes, many patients still display poor prognosis and frequent relapse. Epigenetic alterations contribute to the progression of lymphoma. DNA methylation and histone methylation are the most common epigenetic alterations and regulate the gene expression involved in lymphoma pathogenesis, including silencing of tumor suppressor genes or activation of proto-oncogenes. Dysregulation or mutation of genes related to DNA methylation, including DNMTs, TET2, IDH2, and genes related to histone methylation, including EZH2, KMT2D has been observed. Most of these alterations are associated with inferior outcomes of patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), peripheral T-cell lymphoma (PTCL), and other subtypes of lymphoma. To overcome the pathogenetic consequence induced by aberrant DNA methylation and histone methylation, novel targeted drugs including azacitidine and decitabine have been gradually applied in practice to enhance the efficacy of current therapy and improve the prognosis of lymphoma patients. Investigating and targeting epigenetic mechanisms in lymphoma could be a key point of future research. Therefore, we mainly summarize the methylation alterations in lymphoma and their respective targeted therapies in this review.

Lymphoma cells expressing CD5 (CD5+) confer inferior outcome of diffuse large B-cell lymphoma (DLBCL), especially in non–MYC/BCL2 double expressor (non-DE) patients. In tumor microenvironment, CD5+ non-DE tumor revealed increased proportion of immunosuppressive M2 macrophages and enhanced pathways related to macrophage activation and migration. In accordance to M2 activation, lipid metabolism was upregulated, including fatty acid uptake and fatty acid oxidation, which supplied energy for M2 macrophage polarization and activation. Meanwhile, CD36 expression was upregulated and strongly correlated to the proportion of M2 macrophages in CD5+ non-DE DLBCL. In vitro, a DLBCL cell line (LY10) overexpressing CD5 significantly increased M2 proportion in comparison with control when cocultured with peripheral blood mononuclear cells (PBMCs). The addition of metformin significantly decreased the M2 proportion and the CD36 expression level in the coculture systems, indicating that metformin could target altered lipid metabolism and decrease M2 macrophages in DLBCL, especially in CD5+ non-DE lymphoma. In conclusion, enhanced lipid metabolism and M2 macrophage activation contributed to the immunosuppressive tumor microenvironment and could be potential therapeutic targets in CD5+ non-DE DLBCL.

The control of vortex-induced vibration (VIV) in shear flow with different distributions of Lorentz force is numerically investigated based on the stream function–vorticity equations in the exponential-polar coordinates exerted on moving cylinder for Re = 150. The cylinder motion equation coupled with the fluid, including the mathematical expressions of the lift force coefficient C l , is derived. The initial and boundary conditions as well as the hydrodynamic forces on the surface of cylinder are also formulated. The Lorentz force applied to suppress the VIV has no relationship with the flow field, and involves two categories, i.e., the field Lorentz force and the wall Lorentz force. With the application of symmetrical Lorentz forces, the symmetric field Lorentz force can amplify the drag, suppress the flow separation, decrease the lift fluctuation, and then suppress the VIV while the wall Lorentz force decreases the drag only. With the application of asymmetrical Lorentz forces, besides the above-mentioned effects, the field Lorentz force can increase additional lift induced by shear flow, whereas the wall Lorentz force can counteract the additional lift, which is dominated on the total effect.