Natural killer (NK) cells are known to mediate killing of various cancer types, but tumor cells can develop resistance mechanisms to escape NK cell-mediated killing. Here, we use a “two cell type” whole genome CRISPR-Cas9 screening system to discover key regulators of tumor sensitivity and resistance to NK cell-mediated cytotoxicity in human glioblastoma stem cells (GSC). We identify CHMP2A as a regulator of GSC resistance to NK cell-mediated cytotoxicity and we confirm these findings in a head and neck squamous cells carcinoma (HNSCC) model. We show that deletion of CHMP2A activates NF-κB in tumor cells to mediate increased chemokine secretion that promotes NK cell migration towards tumor cells. In the HNSCC model we demonstrate that CHMP2A mediates tumor resistance to NK cells via secretion of extracellular vesicles (EVs) that express MICA/B and TRAIL. These secreted ligands induce apoptosis of NK cells to inhibit their antitumor activity. To confirm these in vitro studies, we demonstrate that deletion of CHMP2A in CAL27 HNSCC cells leads to increased NK cell-mediated killing in a xenograft immunodeficient mouse model. These findings illustrate a mechanism of tumor immune escape through EVs secretion and identify inhibition of CHMP2A and related targets as opportunities to improve NK cell-mediated immunotherapy.

Car-dependence, Mode-choice, Latent variables, Support vector machine (SVM),

We report the selective-area heteroepitaxial growth of hexagonal boron nitride (h-BN) on graphene layers using catalyst-free chemical vapor deposition. For both catalyst-free and selective-area growth, exfoliated graphene layers were irradiated with a focused ion beam to generate nucleation sites on the inert graphene surface. A high-quality, ultrathin h-BN micropattern array was selectively grown only on the patterned region of graphene using borazine, ammonia, and nitrogen without any metal catalyst. The crystal structure and microstructural properties of h-BN grown on graphene were investigated using synchrotron radiation x-ray diffraction and transmission electron microscopy, respectively. The catalyst-free growth mechanism and heteroepitaxial relationship between h-BN and graphene layers are discussed.

This study aimed to compare the effectiveness of demineralized dentin paste (DDP) with mineral trioxide aggregates(MTA) as a direct pulp capping material. Artificial Class V cavity was prepared to make a pinpoint pulp exposure in a third of the buccal cervical region of maxillary and mandibular right/left canine teeth of six beagle dogs. After bleeding control, (hemostasis was confirmed), MTA (n= 12) was applied to the maxillary and mandibular right canines. DDP (n=12) to the left canines as a control. Superior to the pulpcapped area, the inferior 1/3 of the cavity was filled with resin modified glass ionomer, and the rest of the cavity was filled with a microfilled composite resin using one-step self etching adhesive system. Two, four, and eight weeks later, the dogs were sacrificed and the capped portion was sectioned perpendicularly to the tooth longitudinal axis of tooth to get specimens for microscopic examination. MTA formed a calcific bridge of osteo-dentin in the histological specimens from the dogs sacrificed two, four, and eight weeks later. DDP formed no calcific bridge in the histological specimens from the dogs sacrificed two weeks later but formed a physiologic dentin bridge close to actual dentin, which included dentinal tubules, in those from the dogs sacrificed four, eight weeks later. DDP-using pulp capping led to formation of a physiological dentin bridge and DDP is expected to be applicable as an effective, biocompatible material for direct pulp capping if sealing ability and easiness for handling materials are improved through further research on its properties.

We report the growth of large-scale, single-oriented zinc oxide (ZnO) nanowall networks on epitaxial hexagonal boron nitride (h-BN) films and their application to flexible inorganic ultraviolet (UV) light sensors. Using catalyst-free metal-organic vapor phase epitaxy, ZnO nanowall networks with good vertical alignment are grown on epitaxial h-BN films. The single-oriented crystal structure of the ZnO nanostructures on h-BN is investigated using x-ray diffraction (XRD) spectroscopy, and the heteroepitaxial relationship between ZnO and h-BN is revealed through synchrotron radiation XRD. Interestingly, when utilizing the grown ZnO nanostructure as a channel for UV sensors, better performance merits such as a high IUV/Idark ratio, faster recovery time, and low dark current are achieved if h-BN is employed as a growth template. As an example of inorganic flexible optoelectronic device applications, flexible UV sensors are fabricated using ZnO/h-BN heterostructures owing to the insulating and transferrable nature of h-BN substrates. The sensor maintained an excellent performance, even under highly bent conditions.