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.

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.

A potent phosphodiester Keap1-Nrf2 protein-protein interaction inhibitor as the efficient treatment of Alzheimer's disease.

The Keap1-Nrf2 pathway has been established as a therapeutic target for Alzheimer's disease (AD). Directly inhibiting the protein-protein interaction (PPI) between Keap1 and Nrf2 has been reported as an effective strategy for treating AD. Our group has validated this in an AD mouse model for the first time using the inhibitor 1,4-diaminonaphthalene NXPZ-2 with high concentrations. In the present study, we reported a new phosphodiester containing diaminonaphthalene compound, POZL, designed to target the PPI interface using a structure-based design strategy to combat oxidative stress in AD pathogenesis. Our crystallographic verification confirms that POZL shows potent Keap1-Nrf2 inhibition. Remarkably, POZL showed its high in vivo anti-AD efficacy at a much lower dosage compared to NXPZ-2 in the transgenic APP/PS1 AD mouse model. POZL treatment in the transgenic mice could effectively ameliorate learning and memory dysfunction by promoting the Nrf2 nuclear translocation. As a result, the oxidative stress and AD biomarker expression such as BACE1 and hyperphosphorylation of Tau were significantly reduced, and the synaptic function was recovered. HE and Nissl staining confirmed that POZL improved brain tissue pathological changes by enhancing neuron quantity and function. Furthermore, it was confirmed that POZL could effectively reverse Aß-caused synaptic damage by activating Nrf2 in primary cultured cortical neurons. Collectively, our findings demonstrated that the phosphodiester diaminonaphthalene Keap1-Nrf2 PPI inhibitor could be regarded as a promising preclinical candidate of AD.

Associations of nonconforming gender expression and gender identity with bullying victimization: an analysis of the 2017 youth risk behavior survey.

PURPOSE: Although gender nonconformity (GNC) and transgender identity are both linked to bullying victimization, few studies have examined them with bullying victimization simultaneously. Using a sample of Youth Risk Behavior Survey, we investigated the associations of GNC and transgender identity with bullying victimization within the same study. METHODS: We analyzed data from the cross-sectional school-based Youth Risk Behavior Survey in 2017 (n = 25,378). The exposures were GNC and transgender identity. The main outcomes were traditional victimization, cyber victimization, and combined victimization. We calculated adjusted prevalence ratios (APRs) with 95% confidence intervals (CIs) using Poisson regression models. RESULTS: There were 22.15% of high school students with GNC, and 1.61% identified themselves as transgender. GNC is associated with traditional (APR,1.45;95%CI, 1.21-1.73), cyber (APR,2.00; 95%CI, 1.66-2.40) and combined victimization (APR,1.61;95%CI, 1.42-1.83) respectively among assigned male at birth (AMAB) students only. Transgender male and female students are both at higher risk of bullying victimization for all the three outcomes than cisgender peers. CONCLUSIONS: AMAB GNC and transgender identity are associated with a higher risk of bullying victimization. Providing support systems and celebrating gender diversity within and outside schools are important.

Sodium butyrate ameliorates the cognitive impairment of Alzheimer's disease by regulating the metabolism of astrocytes.

RATIONALE: Energy metabolism disorder is a widespread feature that exists in the early clinical stages of Alzheimer's disease (AD). Astrocyte is the most numerous and the largest glial cell in the brain. By transporting energetic fuels such as lactate and ketones to neurons, astrocytes play a pivotal role in maintaining the cerebral energy homeostasis. Sodium butyrate (NaB), a type of short-chain fatty acid; its anti-inflammatory effect; and inhibition on histone deacetylases have been widely studied. METHODS: Spatial memory and cognitive ability of mice were assessed by using behavioral tests. Western blotting and ELISA kits were used to detect related protein levels and other biochemical markers, respectively. OBJECTIVES: To prove the therapeutic effect of NaB on AD cognitive impairment and provide possible research ideas for mechanism exploration. RESULTS: Administration of NaB could improve the cognitive impairments induced by Aß25-35 in mice. Furthermore, NaB could promote the differentiation of astrocytes towards A2-neuron-protective subtype, astroglial mitochondrial function, and lactate shuttle between astrocytes and neurons. CONCLUSION: These findings reveal the effect of sodium butyrate on astrocytes, which may improve the pathological status of AD and provide experimental basis for sodium butyrate treatment of AD.

The association between chronic bullying victimization with weight status and body self-image: a cross-national study in 39 countries.

BACKGROUND: Childhood obesity and school bullying are pervasive public health issues and known to co-occur in adolescents. However, the association between underweight or thinness and chronic bullying victimization is unclear. The current study examined whether chronic bullying victimization is associated with weight status and body self-image. METHODS: A school-based, cross-sectional study in 39 North American and European countries and regions was conducted. A total of 213,595 adolescents aged 11, 13, and 15 years were surveyed in 2009/10. Chronic bullying victimization was identified using the Revised Olweus Bully/Victim Questionnaire. Weight status was determined using self-reported height and weight and the body mass index (BMI), and body self-image was based on perceived weight. We tested associations between underweight and bullying victimization using three-level logistic regression models. RESULTS: Of the 213,595 adolescents investigated, 11.28% adolescents reported chronic bullying victimization, 14.80% were classified as overweight/obese according to age- and sex-specific BMI criteria, 12.97% were underweight, and 28.36% considered themselves a little bit fat or too fat, 14.57% were too thin. Bullying victimization was less common in older adolescent boys and girls. Weight status was associated with chronic bullying victimization (adjusted ORunderweight = 1.10, 95% CI = 1.05-1.16, p = 0.002; adjusted ORoverweight = 1.40, 95% CI = 1.32-1.49, p < 0.0001; adjusted ORobese = 1.91, 95% CI = 1.71-2.14, p < 0.0001). Body self-image also related to chronic bullying victimization (adjusted ORtoo thin = 1.42, 95% CI = 1.36-1.49, p < 0.0001; adjusted ORa little bit fat = 1.54, 95% CI = 1.48-1.61, p < 0.0001; adjusted ORtoo fat = 3.30, 95% CI = 2.96-3.68, p < 0.0001). CONCLUSION: Both perceived weight and self-rated overweight are associated with chronic bullying victimization. Both overweight and underweight children are at risk of being chronically bullied.

Chinese carless young drivers' self-reported driving behavior and simulated driving performance.

OBJECTIVE: Carless young drivers refers to those drivers aged between 18 and 25 years who have a driver's license but seldom have opportunities to practice their driving skills because they do not have their own cars. Due to China's lower private car ownership, many young drivers become carless young drivers after licensure, and the safety issue associated with them has raised great concern in China. This study aims to provide initial insight into the self-reported driving behaviors and simulated driving performance of Chinese carless young drivers. METHODS: Thirty-three carless young drivers and 32 young drivers with their own cars (as a comparison group) participated in this study. A modified Driver Behavior Questionnaire (DBQ) with a 4-factor structure (errors, violations, attention lapses, and memory lapses) was used to study carless young drivers' self-reported driving behaviors. A simulated driving experiment using a low-cost, fixed-base driving simulator was conducted to measure their simulated driving performance (errors, violations, attention lapses, driving maintenance, reaction time, and accidents). RESULTS: Self-reported DBQ outcomes showed that carless young drivers reported similar errors, more attention lapses, fewer memory lapses, and significantly fewer violation behaviors relative to young drivers with their own cars, whereas simulated driving results revealed that they committed significantly more errors, attention lapses, and violation behaviors than the comparison group. Carless young drivers had a lower ability to maintain the stability of speed and lane position, drove more cautiously approaching and passing through red traffic lights, and committed more accidents during simulated driving. A tendency to speed was not found among carless young drivers; their average speed and speeding frequency were all much lower than that of the comparison group. Lifetime mileage was the only significant predictor of carless young drivers' self-reported violations, simulated violations, speed, and reaction time, whereas no significant predictor was found for young drivers with their own cars. CONCLUSIONS: Carless young drivers had poorer driving performance and were more overconfident of their self-reported driving skills compared to those young drivers with greater access to vehicles. Given that the lifetime mileage positively predicted the simulated violations measure of carless young drivers, immediate interventions are needed to help them increase driving exposure and gain driving experience gradually before moving to more challenging on-road driving tasks. Supplemental materials are available for this article.

An application of the driver behavior questionnaire to Chinese carless young drivers.

OBJECTIVE: Carless young drivers refers to those drivers aged between 18 and 25 years who have a driver's license but seldom have opportunities to practice their driving skills because they do not have their own cars. Due to China's lower private car ownership, many young drivers turn into carless young drivers after licensure, and the safety issue associated with them has become a matter of great concern in China. Because few studies have examined the driving behaviors of these drivers, this study aims to utilize the Driver Behavior Questionnaire (DBQ) to investigate the self-reported driving behaviors of Chinese carless young drivers. METHODS: A total of 523 Chinese carless young drivers (214 females, 309 males) with an average age of 21.91 years completed a questionnaire including the 27-item DBQ and demographics. The data were first randomized into 2 subsamples for factor analysis and then combined together for the following analyses. Both an exploratory factor analysis (EFA, n = 174) and a confirmatory factor analysis (CFA, n = 349) were performed to investigate the factor structure of the DBQ. Correlation analysis was conducted to examine the relationships between the demographics and the DBQ scales' variables. Multivariate linear regression and logistic regression were performed to investigate the prediction of the DBQ scales and crash involvement in the previous year. RESULTS: The EFA produced a 4-factor structure identified as errors, violations, attention lapses, and memory lapses, and the CFA revealed a good model fit after the removal of one item with a low factor loading and the permission of the error covariance between some items. The Chinese carless young drivers reported a comparatively low level of aberrant driving behaviors. The 3 most frequently reported behaviors were all lapses and the 3 least were all violations. Gender was the only significant predictor of the 2 lapses scales and lifetime mileage was the only significant predictor of the violations scale. Only the violations factor was found to be significantly predictive of crash involvement in the previous year. CONCLUSIONS: The current study provides evidence that the DBQ can successfully be utilized to examine the self-reported driving behaviors of Chinese carless young drivers. However, the factor structure as well as the level of reported aberrant driving behaviors suggests that Chinese carless young drivers are a special population and thus should be treated differently when interventions are performed. Supplemental materials are available for this article.