TGF-␤-activated kinase-1 (TAK1), also known as MAPKK kinase-7 (MAP3K7), is a candidate effector of multiple circuits in cardiac biology and disease. Here, we show that inhibition of TAK1 in mice by a cardiac-specific dominant-negative mutation evokes electrophysiological and biochemical properties reminiscent of human Wolff-Parkinson-White syndrome, arising from mutations in AMPactivated protein kinase (AMPK), most notably, accelerated atrioventricular conduction and impaired AMPK activation. To test conclusively the biochemical connection from TAK1 to AMPK suggested by this phenotype, we disrupted TAK1 in mouse embryos and embryonic fibroblasts by Cre-mediated recombination. In TAK1-null embryos, the activating phosphorylation of AMPK at T172 was blocked, accompanied by defective AMPK activity. However, loss of endogenous TAK1 causes midgestation lethality, with defective yolk sac and intraembryonic vasculature. To preclude confounding lethal defects, we acutely ablated floxed TAK1 in culture by viral delivery of Cre. In culture, endogenous TAK1 was activated by oligomycin, the antidiabetic drug metformin, 5-aminoimidazole-4-carboxamide riboside (AICAR), and ischemia, well established triggers of AMPK activity. Loss of TAK1 in culture blocked T172 phosphorylation induced by all three agents, interfered with AMPK activation, impaired phosphorylation of the endogenous AMPK substrate acetyl CoA carboxylase, and also interfered with activation of the AMPK kinase LKB1. Thus, by disrupting the endogenous TAK1 locus, we prove a pivotal role for TAK1 in the LKB1͞AMPK signaling axis, an essential governor of cell metabolism. APKs, MAPKKs (MAP2Ks), and MAP2K kinases (MAP3Ks) comprise a multitiered signaling cascade that couples extracellular cues and intracellular stresses to diverse effector pathways controlling cell growth, survival, transcription, and function (1). Among upstream members of this superfamily, TGF-␤-activated kinase-1 (TAK1)͞MA PKK kinase-7 (MAP3K7) first was identified as a mammalian kinase that complements the lack of Ste11, a MAP3K, in yeast and is activated by TGF-␤ and the relative, bone morphogenetic protein (2). Within the MAPK family, TAK1 is coupled preferentially to JNK and p38. Additional inputs for TAK1 activation include cytokine signaling and innate immunity, and additional outputs include I B kinase ␤ (3). Disruption of TAK1 by saturation mutagenesis in ES cells substantiated that TAK1 is indeed essential for a subset of TGF-␤ effects and also exerts essential functions in signaling by cytokine and Toll-like receptors (3), as proposed on earlier grounds. Additionally, the early-lethal phenotype of TAK1-null embryos, with intraembryonic and yolk sac vascular patterning defects, resembles that of mice devoid of other TGF-␤ signaling proteins, the type I receptor Alk1 and type III receptor endoglin (4).A recognized limitation of germ-line deletions is that potential gene functions may be obscured by early lethality, indirect effects, or secondary adaptations, fueling interest in lineagerestr...

Piezoelectric materials, with their unique ability for mechanical‐electrical energy conversion, have been widely applied in important fields such as sensing, energy harvesting, wastewater treatment, and catalysis. In recent years, advances in material synthesis and engineering have provided new opportunities for the development of bio‐piezoelectric materials with excellent biocompatibility and piezoelectric performance. Bio‐piezoelectric materials have attracted interdisciplinary research interest due to recent insights on the impact of piezoelectricity on biological systems and their versatile biomedical applications. This review therefore introduces the development of bio‐piezoelectric platforms from a broad perspective and highlights their design and engineering strategies. State‐of‐the‐art biomedical applications in both biosensing and disease treatment will be systematically outlined. The relationships between the properties, structure, and biomedical performance of the bio‐piezoelectric materials are examined to provide a deep understanding of the working mechanisms in a physiological environment. Finally, the development trends and challenges are discussed, with the aim to provide new insights for the design and construction of future bio‐piezoelectric materials.

This paper demonstrates the significant benefits of exploiting highly aligned porosity in piezoelectric and pyroelectric materials for improved energy harvesting performance.

No abstract

In this study, aligned porous lead zirconate titanate (PZT) ceramics with high pyroelectric figures-of-merit were successfully manufactured by freeze casting using water-based suspensions. The introduction of aligned pores was demonstrated to have a strong influence on the resultant porous ceramics, in terms of mechanical, dielectric, and pyroelectric properties. As the level of porosity was increased, the relative permittivity decreased, whereas the Curie temperature and dielectric loss increased. The aligned porous structure exhibited improvement in the compressive strength ranging from 19 to 35 MPa, leading to easier handling, better processability and wider applications for such type of porous material. Both types of pyroelectric harvesting figures-of-merit (F E and F 0 E ) of the PZT ceramics with a porosity level of 25-45 vol% increased in all porous ceramics, for example, from 11.41 to 12.43 pJ/m 3 / K 2 and 1.94 to 6.57 pm 3 /J, respectively, at 25°C, which were shown to be higher than the dense PZT counterpart.