NK92 cells and peripheral blood NK cells respond oppositely upon dasatinib treatment.

Natural killer (NK) cell is a valuable tool for immunotherapy in cancer treatment, both the cultured cell line NK92 and primary NK cells are widely studied and used in research and clinical trials. Clinical observations witnessed the improvement of patients' NK cells in terms of cell counts and cytotoxic activity upon dasatinib treatment, an approved drug for chronic myeloid leukaemia and Ph+ acute lymphocytic leukaemia. Several studies supported the clinical observations, yet others argued a detrimental effect of dasatinib on NK cells. Due to the complex conditions in different studies, the definite influence of dasatinib on NK92 and primary NK cells remains to be settled. Here, we used a well-defined in vitro system to evaluate the effects of dasatinib on NK92 cells and peripheral blood (PB)-NK cells. By co-culturing NK cells with dasatinib to test the cell counts and target cell-killing activities, we surprisingly found that the chemical influenced oppositely on these two types of NK cells. While dasatinib suppressed NK92 cell proliferation and cytotoxic activity, it improved PB-NK-killing tumour cells. RNA sequencing analysis further supported this finding, uncovering several proliferating and cytotoxic pathways responding invertedly between them. Our results highlighted an intrinsic difference between NK92 and PB-NK cells and may build clues to understand how dasatinib interacts with NK cells in vivo.

A Building Extraction Method for High-Resolution Remote Sensing Images with Multiple Attentions and Parallel Encoders Combining Enhanced Spectral Information.

Accurately extracting pixel-level buildings from high-resolution remote sensing images is significant for various geographical information applications. Influenced by different natural, cultural, and social development levels, buildings may vary in shape and distribution, making it difficult for the network to maintain a stable segmentation effect of buildings in different areas of the image. In addition, the complex spectra of features in remote sensing images can affect the extracted details of multi-scale buildings in different ways. To this end, this study selects parts of Xi'an City, Shaanxi Province, China, as the study area. A parallel encoded building extraction network (MARS-Net) incorporating multiple attention mechanisms is proposed. MARS-Net builds its parallel encoder through DCNN and transformer to take advantage of their extraction of local and global features. According to the different depth positions of the network, coordinate attention (CA) and convolutional block attention module (CBAM) are introduced to bridge the encoder and decoder to retain richer spatial and semantic information during the encoding process, and adding the dense atrous spatial pyramid pooling (DenseASPP) captures multi-scale contextual information during the upsampling of the layers of the decoder. In addition, a spectral information enhancement module (SIEM) is designed in this study. SIEM further enhances building segmentation by blending and enhancing multi-band building information with relationships between bands. The experimental results show that MARS-Net performs better extraction results and obtains more effective enhancement after adding SIEM. The IoU on the self-built Xi'an and WHU building datasets are 87.53% and 89.62%, respectively, while the respective F1 scores are 93.34% and 94.52%.

1-Naphthaleneacetic Acid Improved the In Vitro Cell Culturing by Inhibiting Apoptosis.

In vitro cell culturing witnessed its applications in scientific research and industrial activities. Attempts to shorten the doubling time of cultured cells have never ceased. In plants, auxin is applied to promote plant growth, the synthetic derivative 1-Naphthaleneacetic acid (NAA) is a good example. Despite the auxin's naturally occurring receptors are not present in mammalian cells, studies suggested they may affect cell culturing. Yet the effects and mechanisms are still unclear. Here, an up to 2-fold increase in the yield of in vitro cultured human cells is observed. Different types of human cell lines and primary cells are tested and found that NAA is effective in all the cells tested. The PI staining followed by FACS suggested that NAA do not affect the cell cycling. Apoptosis-specific dye staining analysis implicated that NAA rescued cell death. Further bulk RNA sequencing is done and it is identified that the lipid metabolism-engaging and anti-apoptosis gene, ANGPTL4, is enhanced in expression upon NAA treatment. Studies on ANGPTL4 knockout cells indicated that ANGPTL4 is required for NAA-mediated response. Thus, the data identified a beneficial role of NAA in human cell culturing and highlighted its potency in in vitro cell culturing.

New role of gramicidin A in RIG-I-like receptors-mediated IFN signalling.

The pattern recognition receptors (PRRs) sense exogenous molecular patterns most commonly derived from invading pathogens, to active the interferon (IFN) signalling. In the cytoplasm, the viral double-stranded RNAs (dsRNAs) are sensed by retinoic acid-inducible gene I (RIG-I) or melanoma differentiation-associated protein 5 (MDA5), depending on the length and chemical properties. Through the binding and oligomerizing onto the RNAs, they form filament to initiate the signalling cascade. Regulation of these receptors' activities are essential for manipulating the strength of IFN signalling. Here, through the virtual screening of chemical reagents using the published MDA5-dsRNA complex structure (PDB: 4GL2), we identified an antibiotic, gramicidin A as a stimulator that enhanced MDA5-mediated IFN signalling. Cytotoxic assay and IFN signalling assay suggested that disruption of lipid membrane, which is a well-defined mechanism of gramicidin A to perform its action, was dispensable in this process. Sucrose gradient ultracentrifugation assay showed that the gramicidin A treatment enhanced MDA5 oligomerization status in the presence of dsRNA. Our work implicated a new role of gramicidin A in innate immunity and presented a new tool to manipulate MDA5 activity.

Current Progress of CAR-NK Therapy in Cancer Treatment.

CD8+ T cells and natural killer (NK) cells eliminate target cells through the release of lytic granules and Fas ligand (FasL)-induced target cell apoptosis. The introduction of chimeric antigen receptor (CAR) makes these two types of cells selective and effective in killing cancer cells. The success of CAR-T therapy in the treatment of acute lymphoblastic leukemia (ALL) and other types of blood cancers proved that the immunotherapy is an effective approach in fighting against cancers, yet adverse effects, such as graft versus host disease (GvHD) and cytokine release syndrome (CRS), cannot be ignored for the CAR-T therapy. CAR-NK therapy, then, has its advantage in lacking these adverse effects and works as effective as CAR-T in terms of killing. Despite these, NK cells are known to be hard to transduce, expand in vitro, and sustain shorter in vivo comparing to infiltrated T cells. Moreover, CAR-NK therapy faces challenges as CAR-T therapy does, e.g., the time, the cost, and the potential biohazard due to the use of animal-derived products. Thus, enormous efforts are needed to develop safe, effective, and large-scalable protocols for obtaining CAR-NK cells. Here, we reviewed current progress of CAR-NK therapy, including its biological properties, CAR compositions, preparation of CAR-NK cells, and clinical progresses. We also discussed safety issues raised from genetic engineering. We hope this review is instructive to the research community and a broad range of readers.

A Simulation and an Experimental Study of Space Harpoon Low-Velocity Impact, Anchored Debris.

The space harpoon is a rigid-flexible, coupled debris capture method with a simple, reliable structure and a high adaptability to the target. For the process of impacting and embedding the harpoon into the target plate, the effect of friction at a low-velocity impact is studied, and the criteria for effective embedding of the harpoon and the corresponding launch velocity are determined. A simulation model of the dynamics of the harpoon and the target plate considering tangential friction is established, and the reliability of the numerical simulation model is verified by comparing the impact test, focusing on the kinetic energy change and embedding length during the impact of the harpoon. The results show that the frictional effect in the low-velocity impact is more obvious for the kinetic energy consumption of the harpoon itself, and the effective embedding of the harpoon into the anchored target ranges from 50~90 mm, corresponding to a theoretical launch initial velocity between 88.4~92.5 m/s.