Inhaled particulate matter 2.5 (PM2.5) can cause lung injury by inducing serious inflammation in lung tissue. Renin-angiotensin system (RAS) is involved in the pathogenesis of inflammatory lung diseases and regulates inflammatory response. Angiotensin-converting enzyme II (ACE2), which is produced through the angiotensin-converting enzyme (ACE)/angiotensin II (Ang II) axis, protects against lung disease. However, few studies have focused on the relationships between PM2.5 and ACE2. Therefore, we aimed to explore the role of ACE2 in PM2.5-induced acute lung injury (ALI). An animal model of PM2.5-induced ALI was established with wild type (C57BL/6, WT) and ACE2 gene knockout (ACE2 KO) mice. The mice were exposed to PM2.5 through intratracheal instillation once a day for 3 days (6.25 mg/kg/day) and then sacrificed at 2 days and 5 days after PM2.5 instillation. The results show that resting respiratory rate (RRR), levels of inflammatory cytokines, ACE and MMPs in the lungs of WT and ACE2 KO mice were significantly increased at 2 days postinstillation. At 5 days postinstillation, the PM2.5-induced ALI significantly recovered in the WT mice, but only partially recovered in the ACE2 KO mice. The results hint that PM2.5 could induce severe ALI through pulmonary inflammation, and the repair after acute PM2.5 postinstillation could be attenuated in the absence of ACE2. Additionally, our results show that PM2.5-induced ALI is associated with signaling p-ERK1/2 and p-STAT3 pathways and ACE2 knockdown could increase pulmonary p-STAT3 and p-ERK1/2 levels in the PM2.5-induced ALI.

Our aims in this study were to examine the positive affect and person-job fit of team members and the effect of their sense of well-being on their job performance. Participants were 212 employees of 10 life insurance companies in Taiwan. We developed a survey to measure employees' positive affect, person-job fit, well-being, and job performance. Results showed that the employees' positive affect had a positive effect on both their sense of well-being and job performance, there was a highly significant positive correlation between person-job fit and well-being, and both well-being and person-job fit had positive effects on job performance. In addition, individuals' positive affect may have directly affected the quality of their job performance and well-being through the indirect effect of the quality of job performance, and person-job fit may have directly affected the quality of job performance, and indirectly affected the quality of job performance through well-being. Therefore, we suggested that managers should emphasize employee positive affect to increase individual employee sense of well-being, thus synchronizing job demands and individual capabilities to improve job performance.

Background: Bone metastasis (BM) is one of the common sites of hepatocellular carcinoma (HCC), and the prognosis of BM patients is worse than patients without it. Our study aimed to identify predictors and prognostic factors of BM in HCC patients and develop two nomograms to quantify the risk of BM and the prognosis of HCC patients with BM. Methods: We retrospectively reviewed the data of patients who were diagnosed as HCC between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. Independent predictors for BM from HCC patients were determined by the univariate and multivariate logistic regression analysis. Independent prognostic factors for HCC patients with BM were identified by univariate and multivariate Cox regression analysis. Two nomograms were established and evaluated by calibration curves, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Results: Nine thousand and forty-seven patients were included. The independent risk factors of BM in newly diagnosed HCC patients are sex, grade, T stage, and N stage. The independent prognostic factors for HCC patients with BM are radiotherapy, chemotherapy, and lung metastasis. The AUC of diagnostic nomogram were 0.726 in the training set and 0.629 in the testing set. For the prognostic nomogram, the AUCs of 6-, 9-, and 12-months were 0.753, 0.799, and 0.732 in the training set and 0.698, 0.770, and 0.823 in the validation set. The calibration curve and DCA indicated the good performance of the nomogram. Conclusions: Two nomograms were established to predict the incidence of BM in HCC patients and the prognosis of HCC patients with BM, respectively. Both nomograms have satisfactory accuracy, and clinical utility may benefit for clinical decision-making.

Mulitdrug resistance (MDR) is one of critical factorslimiting the efficacy of cancer chemoor radiotherapy. Emerging evidence has indicated that MDR is a complex process regulated by multiple factors, among which stress response molecules are considered as central players. AMP-activated protein kinase (AMPK) is a major regulator balancing energy supply and ultimately protects cells from harmful stresses via coordinating multiple metabolic pathways Notably, AMPK activation was recently shown to mediate the metabolism reprogramming in drug resistant cancer cells including promoting Warburg effects and mitochondrial biogenesis. Furthermore, AMPK activity has also been shown to regulate the self-renewal ability of cancer stem cells that are often refractory to chemotherapy. In addition, AMPK phosphorylation was critical in mediating autophagy induction, a process demonstrated to be effective in chemosensitivity modulation via degrading cellular components to satisfy nutrients requirement under stressful condition. Meanwhile, drug discovery targeting AMPK has been developed to validate the pathological significance of AMPK in cancer prevention and treatment. Although conflicting evidence focusing on the AMPK modulation for cancer treatment is still remained, this might be attributed to differences in AMPK isotypes in specific tissues, off-targets effects, the degree and duration of drug administration and experimental setting of stress conditions. This review will focus on AMPK mediated resistance to cancer therapy and discuss its potential therapeutic implication and targeting drug development.

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