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Objective·To investigate the effect of hypoxia inducible factor-1α (HIF-1α) inhibitor YC-1 on the progression of diabetic nephropathy (DN) in mice and the potential mechanism.Methods·Ten-week-old male db/db mice (DN model) and their nondiabetic wild-type (WT) littermates were divided into 4 groups (n=6) according to whether treated with YC-1 or not: WT group, WT+YC-1 group, DB group, and DB+YC-1 group. The treatment groups were intraperitoneally injected with YC-1 (20 mg·kg-1) once a day, while the non-treatment groups received the same volumes of DMSO injection. After a total of 8 weeks of intervention, blood glucose, body weight, and kidney weight of all mice were measured. Serum, urine and kidney tissue samples were harvested. Serum creatinine, urinary albumin-to-creatinine ratio (UACR), and urine neutropil gelatinase-associated lipocalin (NGAL) levels were detected. The kidneys were stained with ‎hemat‎oxyli‎n-eosin (H-E) and periodic acid-Schiff (PAS) to observe the pathological changes. Masson staining was used to detect fibrosis, collagen-Ⅰ was detected by immunohistochemistry, and α-smooth muscle actin (α-SMA) was detected by Western blotting. The expression of HIF-1α was detected by both Western blotting and immunohistochemistry. TUNEL staining and Western blotting for apoptosis-related proteins were used to observe the cell apoptosis level. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were detected by the kits. Endoplasmic reticulum stress (ERS) markers, including immunoglobulin heavy chain binding protein (BiP, also known as GRP78), phospho-protein kinase R-like endoplasmic reticulum kinase (p-PERK), total PERK, phospho-eukaryotic initiation factor 2α (p-eIF2α), total eIF2α, activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP), were determined by Western blotting.Results·Compared with the WT group, the DB group showed significant rise of blood glucose, loss of renal function, severe kidney histopathology injuries and kidney fibrosis, increase of renal HIF-1α expression, and aggravated oxidative stress and ERS. Whilst there were no significant changes in blood glucose, YC-1 treatment notably reduced kidney weight/body weight ratio, serum creatinine, UACR, and urine NGAL levels in db/db mice. YC-1 treatment ameliorated kidney histopathology injuries and kidney fibrosis, and decreased the expressions of collagen-Ⅰ and α-SMA. YC-1 treatment also reduced the number of TUNEL positive cells, the expression of HIF-1α and pro-apoptotic proteins including BAX and cleaved caspase-3, and MDA level in the kidneys of db/db mice, while promoting anti-apoptotic protein BCL-2 expression and SOD activity. The expressions of ERS markers GRP78, p-PERK, p-eIF2α, ATF4, and CHOP were likewise significantly decreased in DB+YC-1 group.Conclusion·HIF-1α inhibitor YC-1 inhibits oxidative stress and abnormal activation of ERS, improving cell apoptosis and fibrosis in the kidneys of DN mice, which would attenuate the aggravation of pathological damage and loss of kidney function.

Pástor and Stambaugh (2012) find that from a forward-looking perspective, stocks are more volatile in the long run than they are in the short run. We demonstrate that when the nonnegative equity premium (NEP) condition is imposed on predictive regressions, stocks are in fact less volatile in the long run, even after taking estimation risk and uncertainties into account. The reason is that the NEP provides an additional parameter identification condition and prior information for future returns. Combined with the mean reversion of stock returns, this condition substantially reduces uncertainty on future returns and leads to lower long-run predictive variance. [ABSTRACT FROM AUTHOR]

This paper aims to investigate how different emotions affect the subsequent index futures returns. We test the forecasting regressions which predict the S&P 500 index futures returns with lagged text‐based emotion (anger, joy, fear, optimism, and gloom) indices and find asymmetric forecasting power exists between pessimism and optimism emotion indices. We show that only the text‐based anger index could reliably perform at predicting index futures return in‐sample and outperform the prevailing unconditional mean out‐of‐sample. Notably, the predictive power of the text‐based anger index persists after controlling for other emotion indices, investor sentiment indices, and fundamental variables known to predict the futures market. And the asset allocation conditioning on text‐based anger index can generate substantial economic benefits. Furthermore, the anger index influences the index futures return through both the discount rate and cash flow channels. [ABSTRACT FROM AUTHOR]

Based on hand‐collected data on Chinese listed non‐state‐owned enterprises (hereafter, non‐SOEs), this paper investigates how political connection and family involvement affect firms' IPO underpricing. We find that political connection and family involvement, serving as common compensatory mechanisms for institutional deficiencies, can significantly alleviate the IPO underpricing of non‐SOEs. Moreover, evidence shows that in regions with a well‐developed institutional environment, political connection significantly reduces the degree of IPO underpricing. But for companies located in regions with a poorer institutional environment, family involvement helps to achieve lower underpricing. The effects also vary with firm size. Political connection significantly mitigates underpricing of large firms. But for small firms, only family involvement plays a significant role in lowering IPO underpricing. Finally, we find that instead of increasing the offering price, the effect works in another way. Non‐SOEs with political connection and family involvement are no longer growth firms, for which the influence of the regulatory bar set by the China Security Regulatory Committee (CSRC) decreases. These firms tend to experience poorer long‐term performance after the IPO. This may lead to a relatively lower price in the secondary market, resulting in a lower level of IPO underpricing. [ABSTRACT FROM AUTHOR]

Using a broad sample of earnings announcements, we show that the initial stock market's response substantially increases and the post‐earnings announcement drift becomes much weaker in the presence of more active pre‐earnings option trading. We find that the strongest initial stock market's response originates from those announcements with higher pre‐earnings option trading, fewer competing announcements, and made on non‐Fridays. Our interpretation is that the heightened investor attention, as captured by higher pre‐earnings option trading, fewer competing announcements, and non‐Friday announcements, accelerates the stock market's response and mitigates the stock market under‐reaction. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationship of soluble CD146 (sCD146) with atherosclerosis and future cardiovascular events in patients with diabetic kidney disease (DKD). Methods A total of 105 DKD patients at chronic kidney disease(CKD) (68 male, 37 female) stage 1-3 were enrolled and another 94 type 2 diabetes mellitus patients without DKD (64 male, 30 female) entered the control group from January 2013 to December 2015 in our hospital. Plasma concentration of sCD146 was measured. Doppler ultrasounds of carotid and lower extremity artery were performed. All the DKD patients were retrospectively followed up (medium follow-up 28 months) .The differences of sCD146 between DKD patients and control group was analyzed and the relationship between sCD146 and proteinuria and renal function was evaluated in DKD patients. The association between sCD146 and atherosclerosis was explored in DKD patients. Kaplan-Meier method was used to evaluate the predictive value of sCD146 in future cardiovascular events. Results The level of sCD146 in diabetes mellitus patients was lower than that of DKD group [the level of sCD146 was (435± 150) and (602 ± 274) µg/L, respectively, t=-5.246, P<0.001]. Spearman analysis showed the positive association between sCD146 and serum creatinine (r=0.36, P<0.001), urinary albumino-to-creatinine ratio (r= 0.225, P=0.001) and its negative correlation with eGFR (r=-0.376, P<0.001). The elevation of sCD146 was further associated with the progression of CKD [the levels of sCD146 in patients of CKD stage 1, 2 and 3 were (472 ± 172), (590 ± 223), (685 ± 340) µg/L, respectively, F=164.203, P<0.001]. In DKD group, the upregulation of sCD146 was associated with both the increase of carotid intima-media thickness (r=0.577, P< 0.001) and femoral intima-media thickness (r=0.765, P<0.001). Patients with higher level of sCD146 tended to have more carotid plaques [OR(95%CI)=17.302(2.752-108.780), P=0.002], unstable carotid plaques [OR (95%CI)=6.404(1.036-39.608), P=0.046] and unstable plaques in lower extremity arteries [OR(95%CI)= 13.641(1.942- 95.825), P=0.009] after the adjustment of other cardiovascular risks. Patients with higher concentration of sCD146 tended to have poorer cardiovascular outcomes (Log rank χ²=9.366, P=0.049). Conclusions The measurement of plasma sCD146 is a noninvasive way which can sensitively reflect the progression of renal function and atherosclerosis, and it can also be a good marker to predict cardiovascular outcomes in DKD patients at CKD stage 1-3. [ABSTRACT FROM AUTHOR]