Our objective was to explore the restorative effect of taurine on experimental nonalcoholic steatohepatitis (NASH). Thirty-six SD rats were randomly divided into three groups, 12 in each group: the normal group was fed standard rat diet; the model group and the treatment group were both fed a high-fat rat diet for 12 weeks, and the rats in the treatment group were simultaneously injected with taurine subcutaneously for 8 weeks. Hepatic histological change was observed; TNF-alpha and TGF-beta(1) protein expression was identified by immunohistochemistry; mRNA expression of TNF-alpha, TGF-beta(1), type I procollagen, and adiponectin was measured by RT-PCR; body weight, weight gain, liver weight, and liver index were measured; and biochemical parameters monitored included serum transaminases, serum lipids, fasting plasma glucose, and hepatic level of oxidative stress. Rats in the model group showed a significant increase in liver weight, liver index, serum transaminase activities, serum triglyceride, fasting plasma glucose, and oxidative stress; the mRNA expression of TNF-alpha, TGF-beta(1), and type I procollagen increased, whereas the expression of adiponectin decreased significantly, compared with that in the normal group. The typical hepatic lesions of NASH were observed histologically in the model group. Taurine treatment resulted in a significant decrease in liver weight, liver index, serum transaminase activities, serum triglyceride, fasting plasma glucose, and oxidative stress; the mRNA expression of TNF-alpha, TGF-beta(1), and type I procollagen decreased, but the expression of adiponectin increased significantly, compared with that in the model group. Histological improvement was observed in the treatment group. In conclusion, taurine could inhibit lipid peroxidation, improve lipid and glucose metabolism, decrease synthesis of TNF-alpha and TGF-beta(1), promote synthesis of adiponectin, and have a restorative effect on experimental NASH.

UC-MSCs could increase IL-4 and promote mobilization of KCs both in vitro and in vivo, subsequently alleviating the liver fibrosis induced by DMN.

Digital piracy is seen as a significant problem for the creative industries. Still, while there have been many academic studies showing that piracy hurts sales, there have been far fewer studies analyzing the effectiveness of anti-piracy measures in reversing this effect. This study attempts to address this question by analyzing how the HADOPI "three strikes" law in France affected digital music sales on the iTunes music store.To do this, we obtained a panel of iTunes sales data from the four major music labels (Universal Music, Warner Music, EMI Music and Sony Music) across a broad set of countries. We then applied a difference-in-difference approach, using sales trends in a control group of European countries to simulate the counterfactual of what music sales in France would have been if HADOPI had not been passed. Our results suggest that increased consumer awareness of HADOPI caused iTunes song and album sales to increase by 22.5% and 25% respectively relative to changes in the control group.In terms of robustness, we find that these sales changes are similar for each of the four major music labels, suggesting that our results are not peculiar to any particular label. We also find that the observed sales increase is much larger in genres that, prior to HADOPI, experienced high piracy levels (e.g., Rap and Hip Hop) than for less pirated genres (e.g., Christian music, classical, and jazz). This strengthens the causal interpretation of our results since if HADOPI is causing pirates to become legitimate purchases, its effects should be stronger for heavily pirated music than it is for other music genres.

Background Nowadays, a positive HBV carrier status is common among pregnant women, especially in endemic areas (such as China), little is known about the impact of maternal HBV infection on the risk of adverse pregnancy outcomes. Pregnant women with HBV infection often develop obstetric complications, such as pregnancy-induced hypertension (PIH) syndrome, postpartum hemorrhage, and gestational diabetes mellitus (GDM), and their infants often exhibit neonatal complications. Methods This study undertook a retrospective cohort analysis to explore the association of HBV carrier status with adverse pregnancy outcomes. A cohort of 85,190 women including 9699 HBsAg-positive and 73,076 HBsAg-negative pregnancies was retrospectively analyzed. Results It’s found that HBsAg-positive pregnancies may result in higher risk of various maternal outcomes such as ICP (OR 3.4,95%CI 2.80 to 4.13), postpartum hemorrhage (OR 1.16,95%CI 1.00 to 1.34). Interestingly, there was a decreased risk of Preeclampsia (OR 0.91,95%CI 0.87 to 0.96), premature rupture of membrane (OR 0.91,95%CI 0.87 to 0.96) and gestational hypertension (OR 0.828,95%CI 0.701 to 0.978). And in vaginal delivery subgroup analysis, It’s found that the HBsAg-positive group had a higher risk of placental abruption (OR, 1.44; 95% CI, 1.16–1.79). Conclusions The present results suggest that compared with HBV positive pregnancies were more likely to be ICP and postpartum hemorrhage. HBV-positive pregnant women underwent vaginal delivery were more likely to have placental abruption and premature birth compared with HBV-negative women. Obstetricians should be aware of ICP, postpartum hemorrhage, placental abruption and premature birth in HBV-positive pregnant women.

Research Summary: This study analyzes how the divestitures that are impelled by activist investors in their campaigns against public corporations affect shareholder value. Using hand-collected data on the activist campaigns that were launched against and the divestitures that were undertaken by Fortune 500 companies between 2007 and 2015, we find that activist-impelled divestitures are more positively associated with immediate and longer-term measures of shareholder value than comparable managerled divestitures. These performance differences persist for nearly two years after the completion of these deals. Our results empirically test the idea that firms with agency problems unlock shareholder value when they divest, and support the notion that activist investors fulfill an important external governance function. Our work also opens new research opportunities and offers practical implications as well. Managerial Summary: This study investigates how divestitures that are undertaken at the behest of activist investors affect shareholder value. We find that divestitures that were undertaken under pressure from activist investors are associated with more positive shareholder returns than comparable divestitures that were undertaken voluntarily by managers. These performance differences persist for nearly two years after the completion of these deals, alleviating concerns about the purported shorttermism of activist investors. Our findings suggest that activist investors may fulfill an important governance † Both authors contributed equally and are listed alphabetically. We sincerely thank Connie Helfat and two anonymous reviewers for their helpful comments and suggestions throughout the review process. We are very grateful to Raffi Amit, Matthew Bidwell,

Growing evidence shows that the inhibitory effect of inflammatory cytokines on new bone formation by osteogenic precursor cells is a critical cause of net bone‐density reduction. Melatonin has been proven to be a potential therapeutic candidate for osteoporosis. However, whether it is capable of antagonizing the suppressing effect of inflammatory cytokines on osteogenic precursor cells is so far elusive. In this study, using the cell culture system of human bone marrow stromal cells and MC3T3‐E1 preosteoblasts, we recorded the following vital observations that provided insights of melatonin‐induced bone formation: 1) melatonin induced bone formation in both normal and inflammatory conditions; 2) Wnt4 was essential for melatonin‐induced bone formation in inflammatory stimulation; 3) melatonin‐ and Wnt4‐induced bone formation occurred via activation of β‐catenin and p38‐JNK MAPK pathways by interaction with a distinct frizzled LDL receptor‐related protein complex; 4) melatonin suppressed the inhibitory effect of NF‐κB on osteogenesis in a Wnt4‐dependent manner; and 5) melatonin induced Wnt4 expression through the ERK1/2‐Pax2‐Egr1 pathway. In summary, we showed a novel mechanism of melatonin‐induced bone formation in an inflammatory environment. Melatonin‐induced Wnt4 expression is essential for its osteoinductive effect and the inhibitory effect of NF‐κB on bone formation. Our novel findings may provide useful information for its potential translational application.—Li, X., Li, Z., Wang, J., Li, Z., Cui, H., Dai, G., Chen, S., Zhang, M., Zheng, Z., Zhan, Z., Liu, H. Wnt4 signaling mediates protective effects of melatonin on new bone formation in an inflammatory environment. FASEB J. 33, 10126–10139 (2019). http://www.fasebj.org

Digital piracy is seen as a significant problem for the creative industries. Still, while there have been many academic studies showing that piracy hurts sales, there have been far fewer studies analyzing the effectiveness of anti-piracy measures in reversing this effect. This study attempts to address this question by analyzing how the HADOPI "three strikes" law in France affected digital music sales on the iTunes music store.To do this, we obtained a panel of iTunes sales data from the four major music labels (Universal Music, Warner Music, EMI Music and Sony Music) across a broad set of countries. We then applied a difference-in-difference approach, using sales trends in a control group of European countries to simulate the counterfactual of what music sales in France would have been if HADOPI had not been passed. Our results suggest that increased consumer awareness of HADOPI caused iTunes song and album sales to increase by 22.5% and 25% respectively relative to changes in the control group.In terms of robustness, we find that these sales changes are similar for each of the four major music labels, suggesting that our results are not peculiar to any particular label. We also find that the observed sales increase is much larger in genres that, prior to HADOPI, experienced high piracy levels (e.g., Rap and Hip Hop) than for less pirated genres (e.g., Christian music, classical, and jazz). This strengthens the causal interpretation of our results since if HADOPI is causing pirates to become legitimate purchases, its effects should be stronger for heavily pirated music than it is for other music genres.

Ferroptosis, as a newly discovered cell death form, has become an attractive target for precision cancer therapy. Several ferroptosis therapy strategies based on nanotechnology have been reported by either increasing intracellular iron levels or by inhibition of glutathione (GSH)-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4). However, the strategy by simultaneous iron delivery and GPX4 inhibition has rarely been reported. Herein, novel tumor microenvironments (TME)-activated metal-organic frameworks involving Fe & Cu ions bridged by disulfide bonds with PEGylation (FCSP MOFs) were developed, which would be degraded specifically under the redox TME, simultaneously achieving GSH-depletion induced GPX4 inactivation and releasing Fe ions to produce ROS via Fenton reaction, therefore causing ferroptosis. More ROS could be generated by the acceleration of Fenton reaction due to the released Cu ions and the intrinsic photothermal capability of FCSP MOFs. The overexpressed GSH and H 2 O 2 in TME could ensure the specific TME self-activated therapy. Better tumor therapeutic efficiency could be achieved by doxorubicin (DOX) loading since it can not only cause apoptosis, but also indirectly produce H 2 O 2 to amplify Fenton reaction. Remarkable anti-tumor effect of obtained FCSP@DOX MOFs was verified via both in vitro and in vivo assays.