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Background The B3 gene family, one of the largest plant-specific transcription factors, plays important roles in plant growth, seed development, and hormones. However, the B3 gene family, especially the REM subfamily, has not been systematically and functionally studied. Results In this study, we performed genome-wide re-annotation of B3 genes in five Solanaceae plants, Arabidopsis thaliana , and Oryza sativa , and finally predicted 1,039 B3 genes, including 231 (22.2%) newly annotated genes. We found a striking abundance of REM genes in pepper species ( Capsicum annuum , Capsicum baccatum , and Capsicum chinense ). Comparative motif analysis revealed that REM and other subfamilies (ABI3/VP1, ARF, RAV, and HSI) consist of different amino acids. We verified that the large number of REM genes in pepper were included in the specific subgroup (G8) through the phylogenetic analysis. Chromosome location and evolutionary analyses suggested that the G8 subgroup genes evolved mainly via a pepper-specific recent tandem duplication on chromosomes 1 and 3 after speciation between pepper and other Solanaceae. RNA-seq analyses suggested the potential functions of REM genes under salt, heat, cold, and mannitol stress conditions in pepper ( C. annuum ). Conclusions Our study provides evolutionary and functional insights into the REM gene family in pepper.

Natural killer (NK) cells are considered potential antitumor effector cells. The aim of this study was to establish a novel type of a chimeric antigen receptor (CAR) NK cell line (CAR-KHYG-1) specific for epidermal growth factor receptor variant III (EGFRvIII)-expressing tumors and investigate the anti-tumor activity of EGFRvIII-specific-CAR-KHYG-1 (EvCAR-KHYG-1). EvCAR-KHYG-1 was established by self-inactivated lentiviral-based transduction of the EvCAR gene and magnetic bead-based purification of EvCAR-expressing NK cells. The anti-tumor effects of EvCAR-KHYG-1 were evaluated using growth inhibition and apoptosis detection assays in glioblastoma (GBM) cell lines (EGFRvIII-expressing and non-expressing U87MG). The findings demonstrated that EvCAR-KHYG-1 inhibited GBM cell-growth via apoptosis in an EGFRvIII-expressing specific manner. This is the first study to establish a CAR NK cell line based on the human NK cell line KHYG-1. Therapy with EvCAR-KHYG-1 may be an effective treatment option for GBM patients.

In infants who have suffered head trauma there are two possible explanations for retinal hemorrhage (RH): direct vitreous shaking and occurrence in association with intracranial lesions. Which possibility is more plausible was examined. This multicenter, retrospective study reviewed the clinical records of children younger than four years with head trauma who had been diagnosed with any findings on head computed tomography (CT) and/or magnetic resonance imaging (MRI). Of 452 cases, 239 underwent an ophthalmological examination and were included in this study. The relationships of RH with intracranial findings and the cause of injury were examined. Odds ratios for RH were significant for subdural hematoma (OR 23.41, p = 0.0004), brain edema (OR 5.46, p = 0.0095), nonaccidental (OR 11.26, p<0.0001), and self-inflicted falls (OR 6.22, p = 0.0041). Although nonaccidental, brain edema and self-inflicted falls were associated with RH, subdural hematoma was most strongly associated with RH.

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults. Natural Killer (NK) cells are potent cytotoxic effector cells against tumor cells inducing GBM cells; therefore, NK cell based- immunotherapy might be a promising target in GBM. T cell immunoglobulin mucin family member 3 (TIM3), a receptor expressed on NK cells, has been suggested as a marker of dysfunctional NK cells. We established TIM3 knockout in NK cells, using the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9). Electroporating of TIM3 exon 2- or exon 5-targeting guide RNA- Cas9 protein complexes (RNPs) inhibited TIM3 expression on NK cells with varying efficacy. T7 endonuclease I mutation detection assays showed that both RNPs disrupted the intended genome sites. The expression of other checkpoint receptors, i.e., programmed cell death 1 (PD1), Lymphocyte-activation gene 3 (LAG3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), and TACTILE (CD96) were unchanged on the TIM3 knockout NK cells. Real time cell growth assays revealed that TIM3 knockout enhanced NK cell–mediated growth inhibition of GBM cells. These results demonstrated that TIM3 knockout enhanced human NK cell mediated cytotoxicity on GBM cells. Future, CRISPR-Cas9 mediated TIM3 knockout in NK cells may prove to be a promising immunotherapeutic alternative in patient with GBM.

In this study, we examine the electrical characteristics of silicon nanowire feedback field-effect transistors (FBFETs) with interface trap charges between the channel and gate oxide. The band diagram, I–V characteristics, memory window, and operation were analyzed using a commercial technology computer-aided design simulation. In an n -channel FBFET, the memory window narrows (widens) from 5.47 to 3.59 V (9.24 V), as the density of the positive (negative) trap charges increases. In contrast, in the p -channel FBFET, the memory window widens (narrows) from 5.38 to 7.38 V (4.18 V), as the density of the positive (negative) trap charges increases. Moreover, we investigate the difference in the output drain current based on the interface trap charges during the memory operation.

Subdural hematoma in infants or toddlers has often been linked to abuse, but it is not clear how many cases actually occur and how many are suspected of abuse. The purpose of this study was to investigate subdural hematoma in infants and toddlers in Japan. This multicenter, retrospective study reviewed the clinical records of children younger than 4 years with head trauma who were diagnosed with any finding on head computed tomography (CT) and/or magnetic resonance imaging (MRI), such as skull fracture and/or intracranial injury. A total of 452 children were included. The group suspected to have been abused was classified as nonaccidental, and the group considered to have been caused by an accident was classified as accidental. Subdural hematoma and other factors were examined on multivariate analysis to identify which factors increase the risk of nonaccidental injuries. Of the 452 patients, 158 were diagnosed with subdural hematoma. Subdural hematoma was the most common finding intracranial finding in head trauma in infants and toddlers. A total of 51 patients were classified into the nonaccidental group, and 107 patients were classified into the accidental group. The age of patients with subdural hematoma showed a bimodal pattern. The mean age of the accidental group with subdural hematoma was significantly older than that in the nonaccidental group (10.2 months vs 5.9 months, respectively. p < 0.001). Multivariate analysis showed that patients under 5 months old, retinal hemorrhage, and seizure were significant risk factors for nonaccidental injury (odds ratio (OR) 3.86, p = 0.0011; OR 7.63, p < 0.001; OR 2.49, p = 0.03; respectively). On the other hand, the odds ratio for subdural hematoma was 1.96, and no significant difference was observed (p = 0.34). At least in Japanese children, infantile subdural hematoma was frequently observed not only in nonaccidental but also in accidental injuries. In infants with head trauma, age, the presence of retinal hemorrhage, and the presence of seizures should be considered when determining whether they were abused. Subdural hematoma is also a powerful finding to detect abuse, but care should be taken because, in some ethnic groups, such as the Japanese, there are many accidental cases.

Objective The medical history of injury given by parents of infants and toddlers with head trauma may not be accurate or completely true. The purpose of this study was to examine the relationship between subdural hematoma (SDH) due to nonaccidental injury and mechanisms of injury provided by caregivers. Methods Our multicenter study group retrospectively reviewed the clinical records of children younger than 4 years with head trauma who have been diagnosed with any finding on head computed tomography (CT) and/or magnetic resonance imaging (MRI). A total of 84 cases of subdural hematomas with retinal findings, including cases reported to the child guidance center and traffic and birth injuries, were included in the study. They were classified by the mechanism of injury provided by the caregivers. Clinical findings were reviewed and classified into nonaccidental and accidental groups. The mechanisms of the injuries were examined by multivariable analysis to identify which ones were statistically associated with nonaccidental injuries. Results Of the 84 patients with SDHs, 51 were classified into the nonaccidental group, and 33 children were classified into the accidental group. In 19 patients with a chief complaint of convulsion who had SDH but no episode of trauma, 18 were classified into the nonaccidental group. On multivariable analysis, unexplained convulsions (odds ratio: 12.04, 95% confidence interval: 1.44-100.49) were significantly associated with increased odds of nonaccidental injury. Conclusions In the present study, there was a relationship between nonaccidental injury and unexplained SDH with a chief complaint of convulsion.

BackgroundAlthough discordance in HER2 positivity between primary and metastatic lesions is well established, changes in HER2 positivity after anti-HER2 therapy have not been well evaluated in gastric cancer. We aimed to evaluate whether HER2 expression in gastric cancer is affected by trastuzumab therapy.MethodsWe enrolled 48 HER2-positive advanced gastric cancer patients treated with trastuzumab-containing first-line chemotherapy and had paired biopsies at baseline and after progression.ResultsAt baseline, HER2 was positive, with immunohistochemistry (IHC) 2+ and in situ hybridization (ISH)+ in five patients, and with IHC 3+ in 43 patients. Fourteen patients (29.1%) exhibited loss of HER2 positivity on post-progression biopsy: 10 with IHC 0 or 1+, and four with IHC 2+/ISH−. HER2 remained positive on second biopsy in 34 patients: four with IHC 2+/ISH+, and 30 with IHC 3+. Median H-scores decreased from 225 to 175 (p = 0.047). HER2 genetic heterogeneity was defined in one of 34 ISH-assessable patients (2.9%) at baseline and seven of 32 (21.9%) at second biopsy. Among 13 patients who received second-line trastuzumab emtansine, three showed HER2-negative conversion; they had no objective response and short progression-free survival (1.2, 1.3, and 3.4 months). Patients with stable HER2 status had a 44% response rate and median progression-free survival of 2.7 (0.4–36.8) months.ConclusionA substantial portion of HER2-positive patients showed HER2-negative conversion with increased HER2 genetic heterogeneity after failure of trastuzumab-containing chemotherapy. Loss of HER2 positivity could be predictive of second-line anti-HER2 treatment, suggesting a need to reexamine HER2 status before initiating second-line anti-HER2 therapy.

A liquid-crystal (LC)-filled transmission electron microscopy (TEM) grid cell coated with the cationic surfactant dodecyltrimethylammonium bromide (DTAB), to which a single-stranded deoxyribonucleic acid probe (ssDNA probe ) was adsorbed at the LC/aqueous interface (TEM DTAB/DNA ), was applied for the highly specific detection of target DNA molecules. The DTAB-coated E7 (used LC mixture) in the TEM grid (TEM DTAB ) exhibited a homeotropic orientation, and changed to a planar orientation upon adsorption of the ssDNA probe . The TEM DTAB/DNA was then exposed to complementary (target) ssDNA, which resulted in a planar-to-homeotropic configurational change of E7 that could be observed through a polarized optical microscope under crossed polarizers. The optimum adsorption density (2 μM) of ssDNA probe enabled the detection of ≥0.05 nM complementary ssDNA. This TEM DTAB/DNA biosensor could differentiate complementary ssDNA from mismatched ssDNA as well as double-stranded DNA. It also successfully detected the genomic DNAs of the bacterium Erwinia carotovora and the fungi Rhazictonia solani . Owe to the high specificity, sensitivity, and label-free detection, this biosensor may broaden the applications of LC-based biosensors to pathogen detection.

Glioblastoma (GBM), which is the most common malignant brain tumor, is resistant to standard treatments. Immunotherapy might be a promising alternative for the treatment of this cancer. Chimeric antigen receptor (CAR) is an artificially modified fusion protein that can be engineered to direct the specificity and function of T cells against tumor antigens. However, the antitumor effects of EGFRvIII-targeting CAR-T (EvCAR-T) cells in GBM are limited. The inhibitory effect is induced by the interaction between programmed cell death protein 1 (PD-1) on activated EvCAR-T cells and its ligands on GBM cells. In the present study, PD-1-disrupted EvCAR-T cells were established using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9). The sgRNA/Cas9 expression vectors designed precisely disrupted the target region of PD-1 and inhibited the expression of PD-1 in EvCAR-T cells. The PD-1-disrupted EvCAR-T cells had an in vitro growth inhibitory effect on EGFRvIII-expressing GBM cells without altering the T-cell phenotype and the expression of other checkpoint receptors. In the future, the in vivo antitumor effect of this vector should be evaluated in order to determine if it could be applied clinically for improving the efficacy of EvCAR-T cell-based adoptive immunotherapy for GBM.