No abstract

A large‐scale survey study was conducted to assess trauma, burnout, posttraumatic growth, and associated factors for nurses in the COVID‐19 pandemic. The Trauma Screening Questionnaire, Maslach Burnout Inventory, and Posttraumatic Growth Inventory‐Short Form were utilized. Factors associated with trauma, burnout, and posttraumatic growth were analysed using logistic and multiple regressions. In total, 12 596 completed the survey, and 52.3% worked in COVID‐19 designated hospitals. At the survey’s conclusion in April, 13.3% reported trauma (Trauma ≥ 6), there were moderate degrees of emotional exhaustion, and 4,949 (39.3%) experienced posttraumatic growth. Traumatic response and emotional exhaustion were greater among (i) women (odds ratio [OR]: 1.48, 95% CI 1.12–1.97 P = 0.006; emotional exhaustion OR: 1.30, 95% CI 1.09–1.54, P = 0.003), (ii) critical care units (OR: 1.20, 95% CI 1.06–1.35, P = 0.004; emotional exhaustion OR: 1.23, 95% CI 1.12–1.33, P < 0.001) (iii) COVID‐19 designated hospital (OR: 1.24, 95% CI 1.11–1.38; P < 0.001; emotional exhaustion OR: 1.26, 95% CI 1.17–1.36; P < 0.001) and (iv) COVID‐19‐related departments (OR: 1.16, 95% CI 1.04–1.29, P = 0.006, emotional exhaustion only). To date, this is the first large‐scale study to report the rates of trauma and burnout for nurses during the COVID‐19 pandemic. The study indicates that nurses who identified as women, working in ICUs, COVID‐19 designated hospitals, and departments involved with treating COVID‐19 patients had higher scores in mental health outcomes. Future research can focus on the factors the study has identified that could lead to more effective prevention and treatment strategies for adverse health outcomes and better use of resources to promote positive outcomes.

No abstract

AbstractMethyltransferase-like 3 (METTL3) was originally known to be responsible for N6-methyladenosine (m6A) modification of mRNA. Recent studies have found that METTL3 plays important roles in a variety of tumors by regulating the translation of oncogenes. However, the functional and regulating mechanisms of METTL3 in human gastric cancer have not yet been understood. Here we knocked down METTL3 in human gastric cancer cell lines, AGS and MKN45, by using shRNA transfection. RT-qPCR assay and western blotting verified the effectiveness of RNA interference on mRNA and protein levels, respectively. Then we found that METTL3 knockdown inhibited cell proliferation, migration and invasion in AGS and MKN45 cells. Moreover, METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. Mechanistic investigation suggested that METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors p70S6K and Cyclin D1. In conclusion, our study reveals that down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 may be a potential target for the treatment of human gastric cancer.

Accumulating evidence has indicated that activation of microglia and neuroinflammation reaction play a prominent role in Alzheimer's disease (AD). Inhibition of toll-like receptor 4 (TLR4) has been shown to be associated with immune responses and brain damage, but its effects on AD remain unclear. This study mainly aimed to investigate the protective effect of TAK-242 (TLR4-specific inhibitor) on microglial polarization and neuroprotection in an AD mouse model and the underlying mechanisms. We found that APP/PS1 transgenic AD mice exhibited a dramatic increase in TLR4 levels concomitant with a significantly higher expression of inflammatory microglia compared to C57BL/6 wildtype mice. Furthermore, inhibition of TLR4 by TAK-242 administration significantly improved neurological function, decreased the level of Bax, and caused a significant reduction in the levels of M1-markers (iNOS and TNFα), while the expressions of M2-phenotype markers (Trem-2 and Arg-1) were increased both in vivo and in vitro. Furthermore, TAK-242 treatment enhanced BV2 microglial phagocytosis. Moreover, Aβ 25−35 caused the upregulation of inflammatory cytokine production, MyD88, NF-kappaB-p65, and NLRP3, which could be ameliorated by NLRP3-siRNA or TAK-242. These findings indicated that TLR4 inhibition provided neuroprotection and promoted a microglial switch from the inflammatory M1 phenotype to the protective M2 phenotype in AD. The mechanism involved may be related to modulation of the MyD88/NF-kappaB/NLRP3 signaling pathway.