Rui Chen

as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size control, and regeneration. The core of the Hippo pathway in mammals consists of a kinase cascade, MST1/2 and LATS1/2, as well as downstream effectors, transcriptional coactivators YAP and TAZ. These core components of the Hippo pathway control transcriptional programs involved in cell proliferation, survival, mobility, stemness, and differentiation. The Hippo pathway is tightly regulated by both intrinsic and extrinsic signals, such as mechanical force, cell-cell contact, polarity, energy status, stress, and many diffusible hormonal factors, the majority of which act through G protein-coupled receptors. Here, we review the current understanding of molecular mechanisms by which signals regulate the Hippo pathway with an emphasis on mechanotransduction and the effects of this pathway on basic biology and human diseases.

Characterized by ventricular dilatation, systolic dysfunction, and progressive heart failure, dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy in patients. DCM is the most common diagnosis leading to heart transplantation and places a significant burden on healthcare worldwide. The advent of induced pluripotent stem cells (iPSCs) offers an exceptional opportunity for creating disease-specific cellular models, investigating underlying mechanisms, and optimizing therapy. Here, we generated cardiomyocytes from iPSCs derived from patients in a DCM family carrying a point mutation (R173W) in the gene encoding sarcomeric protein cardiac troponin T. Compared to control healthy individuals in the same family cohort, cardiomyocytes derived from iPSCs from DCM patients exhibited altered regulation of calcium ion (Ca(2+)), decreased contractility, and abnormal distribution of sarcomeric α-actinin. When stimulated with a β-adrenergic agonist, DCM iPSC-derived cardiomyocytes showed characteristics of cellular stress such as reduced beating rates, compromised contraction, and a greater number of cells with abnormal sarcomeric α-actinin distribution. Treatment with β-adrenergic blockers or overexpression of sarcoplasmic reticulum Ca(2+) adenosine triphosphatase (Serca2a) improved the function of iPSC-derived cardiomyocytes from DCM patients. Thus, iPSC-derived cardiomyocytes from DCM patients recapitulate to some extent the morphological and functional phenotypes of DCM and may serve as a useful platform for exploring disease mechanisms and for drug screening.

China is one of the few countries with some of the highest particulate matter levels in the world. However, only a small number of particulate matter health studies have been conducted in China. The study objective was to examine the association of particulate matter with an aerodynamic diameter of less than 10 μm (PM(10)) with daily mortality in 16 Chinese cities between 1996 and 2008. Two-stage Bayesian hierarchical models were applied to obtain city-specific and national average estimates. Poisson regression models incorporating natural spline smoothing functions were used to adjust for long-term and seasonal trends of mortality, as well as other time-varying covariates. The averaged daily concentrations of PM(10) in the 16 Chinese cities ranged from 52 μg/m(3) to 156 μg/m(3). The 16-city combined analysis showed significant associations of PM(10) with mortality: A 10-μg/m(3) increase in 2-day moving-average PM(10) was associated with a 0.35% (95% posterior interval (PI): 0.18, 0.52) increase of total mortality, 0.44% (95% PI: 0.23, 0.64) increase of cardiovascular mortality, and 0.56% (95% PI: 0.31, 0.81) increase of respiratory mortality. Females, older people, and residents with low educational attainment appeared to be more vulnerable to PM(10) exposure. Conclusively, this largest epidemiologic study of particulate air pollution in China suggests that short-term exposure to PM(10) is associated with increased mortality risk.