The role of DHX15, a newly identified DEAH-box RNA helicase, in leukemogenesis remains elusive. Here, we identified a recurrent mutation in DHX15 (NM_001358:c.664C>G: p.(R222G)) in one familial AML patient and 4/240 sporadic AML patients. Additionally, DHX15 was commonly overexpressed in AML patients and associated with poor overall survival (OS) (P=0.019) and relapse-free survival (RFS) (P=0.032). In addition, we found a distinct expression pattern of DHX15. DHX15 was highly expressed in hematopoietic stem cells and leukemia cells but was lowly expressed in mature blood cells. DHX15 was down-regulated when AML patients achieved disease remission or when leukemia cell lines were induced to differentiate. DHX15 silencing greatly inhibited leukemia cell proliferation and induced cell apoptosis and G1-phase arrest. In contrast, the restoration of DHX15 expression rescued cell viability and reduced cell apoptosis. In addition, we found that DHX15 was down-regulated when cell apoptosis was induced by ATO (arsenic trioxide); overexpression of DHX15 caused dramatic resistance to ATO-induced cell apoptosis, suggesting an important role for DHX15 in cell apoptosis. We further explored the mechanism of DHX15 in apoptosis and found that overexpression of DHX15 activated NF-kB transcription. Knockdown of DHX15 inhibited the nuclear translocation and activation of the NF-kB subunit P65 in leukemia cells. Several downstream targets of the NF-kB pathway were also down-regulated, and apoptosis-associated genes CASP3 and PARP were activated. In conclusion, this study represents the first demonstration that DHX15 plays an important role in leukemogenesis via the NF-kB signaling pathway and may serve as an independent prognostic marker for AML.

SARS-coronavirus-2–induced immune dysregulation and inflammatory responses are involved in the pathogenesis of coronavirus disease-2019 (COVID-19). However, very little is known about immune cell and cytokine alterations in specific organs of COVID-19 patients. Here, we evaluated immune cells and cytokines in postmortem tissues, i.e., lungs, intestine, liver, kidneys, and spleen of three patients with COVID-19. Imaging mass cytometry revealed monocyte, macrophage, and dendritic cell (DC) infiltration in the lung, intestine, kidney, and liver tissues. Moreover, in patients with COVID-19, natural killer T cells infiltrated the liver, lungs, and intestine, whereas B cells infiltrated the kidneys, lungs, and intestine. CD11b+ macrophages and CD11c+ DCs also infiltrated the lungs and intestine, a phenomenon that was accompanied by overproduction of the immunosuppressive cytokine interleukin (IL)-10. However, CD11b+ macrophages and CD11c+ DCs in the lungs or intestine of COVID-19 patients did not express human leukocyte antigen DR isotype. In contrast, tumor necrosis factor (TNF)-α expression was higher in the lungs, intestine, liver, and kidneys, but not in the spleen, of all COVID-19 patients (compared to levels in controls). Collectively, these findings suggested that IL-10 and TNF-α as immunosuppressive and pro-inflammatory agents, respectively,—might be prognostic and could serve as therapeutic targets for COVID-19.

ASXL1 mutations were associated with poor prognosis in MDS, which may contribute to risk stratification and prognostic assessment in the disease.

Detecting the light from different freedom is of great significance to gain more information. Two-dimensional (2D) materials with low intrinsic carrier concentration and highly tunable electronic structure have been considered as the promising candidate for future room-temperature multi-functional photodetectors. However, current investigations mainly focus on intensity-sensitive detection; the multi-dimensional photodetection such as polarization-sensitive photodetection is still in its early stage. Herein, the intensity-and polarization-sensitive photodetection based on α-In 2 Se 3 is studied. By using angle-resolved polarized Raman spectroscopy, it is demonstrated that α-In 2 Se 3 shows an anisotropic phonon vibration property indicating its asymmetric structure. The α-In 2 Se 3 -based photodetector has a photoelectric performance with a responsivity of 1936 A/W and a specific detectivity of 2.1 × 10 13 Jones under 0.2 mW/cm 2 power density at 400 nm. Moreover, by studying the polarized angleresolved photoelectrical effect, it is found that the ratio of maximum and minimum photocurrent (dichroic ratio) reaches 1.47 at 650 nm suggesting good polarization-sensitive detection. After post-annealing, α-In 2 Se 3 in situ converts to β-In 2 Se 3 which has similar inplane anisotropic crystallinity and exhibits a dichroic ratio of 1.41. It is found that the responsivity of β-In 2 Se 3 is 6 A/W, much lower than that of α-In 2 Se 3 . The high-performance light intensity-and polarization-detection of α-In 2 Se 3 enlarges the 2D anisotropic materials family and provides new opportunities for future dual-mode photodetection.