Sodium/glucose cotransporter-2 inhibitors (SGLT2i) are a new type of glucose-lowering drug that can reduce blood glucose by inhibiting its reabsorption in proximal tubules and by promoting urinary glucose excretion. SGLT2i are widely used in the clinical treatment of type 2 diabetes mellitus (T2DM). In recent studies, SGLT2i were found to not only reduce blood glucose but also protect the heart and kidney, which can significantly reduce cardiovascular events, delay the progression of renal failure, greatly improve the quality of life of patients, and reduce medical expenses for families and society. As adverse cardiac and renal events are the most common and serious complications of T2DM, it is very important to understand the cardio- and renoprotective mechanisms of SGLT2i. This article reviews the historical development, pharmacological mechanism, heart and kidney protection and safety of SGLT2i. The information presented provides a theoretical basis for the clinical prevention and treatment of diabetes and its complications and for the development of new glucose-lowering drugs.

Oxygen vacancy (VO) plays the critical role for resistive switching in transition metal oxide resistive random access memory (RRAM). First principles calculation is performed to study the impact of metallic ion (Al, Ti, or La) doping in ZrO2 on the behaviors of VO, including defect energy level and formation energy (Evf). Trivalent dopant (Al or La) significantly reduces Evf. Based on the calculated results, ZrO2-based RRAM devices are designed to control the formation of VO, and improved resistive switching uniformity is demonstrated in experiments.

Highlights d TNIP3 expression is negatively correlated with NASH development in humans d Transgenic TNIP3 expression alleviates NASH in mice d TNIP3 blunts NASH progression by blocking TRIM8mediated TAK1 activation d Adenoviral-mediated hepatic TNIP3 overexpression

Younger and older American and Chinese adults were administered arithmetic, perceptual speed, and spatial orientation tests. For the perceptual speed and spatial orientation tests, the younger adults showed substantial performance advantages over the older adults in both the United States and China. For the arithmetic tests, the younger Chinese adults outperformed the older Chinese adults, but the groups of younger and older American adults had comparable arithmetical abilities. Cross-national comparisons indicated that the younger Chinese adults outperformed the younger American adults on the arithmetic tests, but not on the perceptual speed and spatial orientation tests. The performance of the older American and older Chinese adults was comparable for all of the ability measures. The overall pattern suggests that the advantage of Chinese adults over American adults in complex arithmetic might be a relatively recent phenomenon. The first systematic cross-national study of mathematical abilities was conducted in 1964 (Hus~n, 1967). The results of this study showed that American adolescents were among the most poorly educated students in mathematics in the industrialized world. In the ensuing 30 years, this basic finding has been replicated many times and has been shown to be true for nearly all mathematical domains, from arithmetic to complex mathematics (Crosswhite, Dossey, Swafford, McKnight, & Cooney, 1985; Lapointe, Mead, & Askew, 1992). Differences between the mathematical development of American children and children from other nations are often times most extreme when comparisons are made between the United States and East Asian nations (i.e., China, Korea, Taiwan, & Japan; e.g., Stevenson, Chen, & Lee, 1993; Stevenson et al., 1990)J The consistency of academic achievement differences between children from the United States and children from East Asian nations has led some scientists to argue that these differences stem